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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02795767




Registration number
NCT02795767
Ethics application status
Date submitted
7/06/2016
Date registered
10/06/2016

Titles & IDs
Public title
A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors
Scientific title
A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With Inhibitors
Secondary ID [1] 0 0
2016-000073-21
Secondary ID [2] 0 0
BH29992
Universal Trial Number (UTN)
Trial acronym
HAVEN 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Emicizumab

Experimental: Cohort A: 1.5 mg/kg Emicizumab QW - Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Experimental: Cohort B: 3 mg/kg Emicizumab Q2W - Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Experimental: Cohort C: 6 mg/kg Emicizumab Q4W - Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.


Treatment: Drugs: Emicizumab
Emicizumab will be administered as per the schedule specified in the respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [1] 0 0
The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [1] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [2] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [2] 0 0
The number of all bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [2] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [3] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [3] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [3] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [4] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [4] 0 0
The number of treated joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [4] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [5] 0 0
Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [5] 0 0
The number of treated target joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [5] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [6] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [6] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [6] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [7] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [7] 0 0
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [7] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [8] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [8] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [8] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [9] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [9] 0 0
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [9] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [10] 0 0
Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [10] 0 0
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [10] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [11] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [11] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [11] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [12] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [12] 0 0
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [12] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [13] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [13] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [13] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [14] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [14] 0 0
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [14] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [15] 0 0
Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [15] 0 0
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [15] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [16] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [16] 0 0
The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [16] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [17] 0 0
Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [17] 0 0
The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [17] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [18] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [18] 0 0
The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [18] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [19] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [19] 0 0
The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [19] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Primary outcome [20] 0 0
Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [20] 0 0
The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [20] 0 0
From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Secondary outcome [1] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [1] 0 0
The number of treated bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [1] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [2] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [2] 0 0
The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [2] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [3] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [3] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [3] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [4] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [4] 0 0
The number of treated joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [4] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [5] 0 0
Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [5] 0 0
The number of treated target joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [5] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [6] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [6] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [6] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [7] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [7] 0 0
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [7] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [8] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [8] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [8] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [9] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [9] 0 0
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [9] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [10] 0 0
Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [10] 0 0
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [10] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [11] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Assessment method [11] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [11] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [12] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Assessment method [12] 0 0
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [12] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [13] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Assessment method [13] 0 0
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [13] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [14] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [14] 0 0
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [14] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [15] 0 0
Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [15] 0 0
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [15] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [16] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [16] 0 0
The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [16] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [17] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [17] 0 0
The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [17] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [18] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [18] 0 0
The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Timepoint [18] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [19] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [19] 0 0
The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Timepoint [19] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [20] 0 0
Cohorts B and C: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Assessment method [20] 0 0
The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Timepoint [20] 0 0
From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Secondary outcome [21] 0 0
Cohort A: Intra-Participant Comparison of the Model-Based ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the Non-Interventional Study (NIS) Population
Assessment method [21] 0 0
This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for treated bleeds (i.e., number of treated bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [21] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [22] 0 0
Cohort A: Intra-Participant Comparison of the Model-Based ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Assessment method [22] 0 0
This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for all bleeds (i.e., number of all bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [22] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [23] 0 0
Cohort A: Intra-Participant Comparison of the Median Calculated ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Assessment method [23] 0 0
This is an intra-participant comparison of the calculated ABR for treated bleeds (annualized per participant using the following formula: ABR = \[number of bleeds/number of days during the efficacy period\] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [23] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [24] 0 0
Cohort A: Intra-Participant Comparison of the Median Calculated ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Assessment method [24] 0 0
This is an intra-participant comparison of the calculated annualized bleeding rate (ABR) for all bleeds (annualized for each participant using the following formula: ABR = \[number of bleeds/number of days during the efficacy period\] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [24] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [25] 0 0
Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Assessment method [25] 0 0
This is an intra-participant comparison of the percentage of participants by categorized number of treated bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [25] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [26] 0 0
Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Assessment method [26] 0 0
This is an intra-participant comparison of the percentage of participants by categorized number of all bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [26] 0 0
Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Secondary outcome [27] 0 0
Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Assessment method [27] 0 0
The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [27] 0 0
From Baseline to 52 weeks
Secondary outcome [28] 0 0
Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Assessment method [28] 0 0
The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [28] 0 0
From Baseline to 52 weeks
Secondary outcome [29] 0 0
Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Assessment method [29] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [29] 0 0
From Baseline to 52 weeks
Secondary outcome [30] 0 0
Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants =12 Years of Age and <40 kg Body Weight
Assessment method [30] 0 0
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [30] 0 0
From Baseline to 52 weeks
Secondary outcome [31] 0 0
Number of Treated Bleeds Over Time in Participants With Dose Up-Titration
Assessment method [31] 0 0
The number of treated bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Timepoint [31] 0 0
From Baseline to study completion (up to at least 52 weeks)
Secondary outcome [32] 0 0
Number of All Bleeds Over Time in Participants With Dose Up-Titration
Assessment method [32] 0 0
The number of all bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Timepoint [32] 0 0
From Baseline to study completion (up to at least 52 weeks)
Secondary outcome [33] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [33] 0 0
The number of bleeds over the efficacy period was shown as a model-based ABR that used a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed occurring in a joint. A "target joint bleed" is defined as a joint bleed in a target joint (=3 bleeds have occurred over the last 24 weeks prior to study entry).
Timepoint [33] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [34] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [34] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Timepoint [34] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [35] 0 0
Long-Term Efficacy of Emicizumab in All Cohorts: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Assessment method [35] 0 0
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Timepoint [35] 0 0
From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Secondary outcome [36] 0 0
Change From Baseline Over Time in the Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score, as Completed by Treated Participants =8 to <12 Years of Age
Assessment method [36] 0 0
The Haemo-QoL-SF is a self-reported questionnaire for children =8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and ranges from 0 to 100, with a lower score reflective of better health-related quality of life.
Timepoint [36] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [37] 0 0
Change From Baseline Over Time in the Haemo-QoL-SF Questionnaire Physical Health Domain Score, as Completed by Treated Participants =8 to <12 Years of Age
Assessment method [37] 0 0
The Haemo-QoL-SF is a self-reported questionnaire for children =8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. The Physical Health domain assesses hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement). Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Physical Health domain score ranges from 0 to 100, with a lower score reflective of better physical health.
Timepoint [37] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [38] 0 0
Change From Baseline Over Time in Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors Including Aspects of Caregiver Burden (Adapted Inhib-QoL) Questionnaire Total Score, Treated Participants <12 Years of Age
Assessment method [38] 0 0
Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. The Total Score is derived from the individual scores of all of the domains and it ranges from 0 to 100, with lower scores reflective of better HRQoL.
Timepoint [38] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [39] 0 0
Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age
Assessment method [39] 0 0
Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL (proxy HRQoL) and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family Life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. A total score is calculated as the sum of all of the items in the scale. The Physical Health domain score ranges from 0 to 100, with lower scores reflective of better physical health.
Timepoint [39] 0 0
Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Secondary outcome [40] 0 0
Number of Participants With at Least One Adverse Event
Assessment method [40] 0 0
The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, are reported.
Timepoint [40] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [41] 0 0
Number of Participants With at Least One Grade =3 Adverse Event
Assessment method [41] 0 0
The World Health Organization (WHO) toxicity grading scale was used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable.
Timepoint [41] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [42] 0 0
Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment
Assessment method [42] 0 0
Timepoint [42] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [43] 0 0
Number of Participants With at Least One Adverse Event of Local Injection Site Reaction
Assessment method [43] 0 0
Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction."
Timepoint [43] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [44] 0 0
Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction
Assessment method [44] 0 0
Systemic hypersensitivity, anaphylaxis, or anaphylactoid reactions were identified by the investigator using Sampson's criteria, as defined in the protocol. At the primary completion date, one participant had reported two non-serious adverse events (cough and abdominal pain) that were identified as a potential case based on a Standardised MedDRA Queries (SMQ) search for Sampson's criteria. However, after medical review of the case, it was confirmed that this case was not indicative of a systemic hypersensitivity, anaphylaxis, or anaphylactoid reaction.
Timepoint [44] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [45] 0 0
Number of Participants With at Least One Adverse Event of Thromboembolic Event
Assessment method [45] 0 0
Timepoint [45] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [46] 0 0
Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy
Assessment method [46] 0 0
Timepoint [46] 0 0
From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Secondary outcome [47] 0 0
Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study
Assessment method [47] 0 0
'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a =4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a =4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.
Timepoint [47] 0 0
Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)
Secondary outcome [48] 0 0
Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Assessment method [48] 0 0
The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count
Timepoint [48] 0 0
From Baseline until study completion (up to 188 weeks)
Secondary outcome [49] 0 0
Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Assessment method [49] 0 0
The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for chemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Timepoint [49] 0 0
From Baseline until study completion (up to 188 weeks)
Secondary outcome [50] 0 0
Plasma Trough Concentration (Ctrough) of Emicizumab
Assessment method [50] 0 0
Pre-dose (trough) plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was 0.1 micrograms per milliliter (µg/mL).
Timepoint [50] 0 0
Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177

Eligibility
Key inclusion criteria
* Children less than (<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh <40 kilograms (kg) (Cohort A only); and participants <2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)
* Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is [i.e.], greater than or equal to [>/=] 5 bethesda units [BU])
* Requires treatment with bypassing agents
* Adequate hematologic, hepatic, and renal function
Minimum age
No limit
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inherited or acquired bleeding disorder other than hemophilia A
* Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII
* Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
* Other disease that may increase risk of bleeding or thrombosis
* History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection
* Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus
* Use of systemic immunomodulators at enrollment or planned use during the study period
* Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
* Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)
* Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/11/2020
Sample size
Target
Accrual to date
Final
88
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Costa Rica
State/province [9] 0 0
San Jose
Country [10] 0 0
France
State/province [10] 0 0
Bron
Country [11] 0 0
France
State/province [11] 0 0
Le Kremlin Bicetre
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
Germany
State/province [13] 0 0
Bonn
Country [14] 0 0
Italy
State/province [14] 0 0
Lombardia
Country [15] 0 0
Japan
State/province [15] 0 0
Aichi
Country [16] 0 0
Japan
State/province [16] 0 0
Kitakyushu-shi
Country [17] 0 0
Japan
State/province [17] 0 0
Nara
Country [18] 0 0
Japan
State/province [18] 0 0
Shizuoka
Country [19] 0 0
Japan
State/province [19] 0 0
Tokyo
Country [20] 0 0
South Africa
State/province [20] 0 0
Johannesburg
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Sevilla
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
Turkey
State/province [24] 0 0
Adana
Country [25] 0 0
Turkey
State/province [25] 0 0
Istanbul
Country [26] 0 0
Turkey
State/province [26] 0 0
Izmir
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Chugai Pharmaceutical
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02795767