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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02847637




Registration number
NCT02847637
Ethics application status
Date submitted
26/07/2016
Date registered
28/07/2016
Date last updated
16/11/2022

Titles & IDs
Public title
A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors
Scientific title
A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients Without Inhibitors
Secondary ID [1] 0 0
2016-000072-17
Secondary ID [2] 0 0
BH30071
Universal Trial Number (UTN)
Trial acronym
HAVEN 3
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
Description of intervention(s) / exposure
Treatment: Drugs - Emicizumab
Treatment: Drugs - Factor VIII (FVIII)

Active Comparator: Arm C (Control): No Prophylaxis, Then Emicizumab - Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial. After completing 24 weeks of no prophylaxis (i.e., episodic FVIII treatment) on study, then they were given the opportunity to switch to emicizumab prophylaxis of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.

Experimental: Arm A: Emicizumab 1.5 mg/kg QW - Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram (mg/kg) subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.

Experimental: Arm B: Emicizumab 3 mg/kg Q2W - Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 3 mg/kg emicizumab SC once every 2 weeks (Q2W). Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.

Experimental: Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) - Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg subcutaneously (SC) once per week (QW) for 4 weeks, followed by maintenance dosing of 1.5 mg/kg emicizumab SC QW. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted and continue on that dosing regimen until discontinuation from the study.


Treatment: Drugs: Emicizumab
Participants received emicizumab prophylaxis subcutaneously at the specified dose for each arm. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol version 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant had the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg once every 4 weeks [Q4W]) and continue on that dosing regimen until discontinuation from the study.

Treatment: Drugs: Factor VIII (FVIII)
FVIII was allowed to treat bleeds on an episodic basis, per the local prescribing information. Specific dosages of FVIII were not mandated in the study. Breakthrough bleeds were to be treated with the lowest FVIII dose expected to achieve hemostasis, which may have been lower than the participant's prior FVIII dose. To avoid bleeds before adequate emicizumab level is reached, patients in Arm D continued their regular FVIII prophylaxis until the second emicizumab loading dose. Concomitant routine FVIII prophylaxis was not permissible otherwise during the study.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Bleeding Rate (ABR) for Treated Bleeds
Timepoint [1] 0 0
From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks)
Secondary outcome [1] 0 0
Annualized Bleeding Rate (ABR) for All Bleeds
Timepoint [1] 0 0
From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks)
Secondary outcome [2] 0 0
Annualized Bleeding Rate (ABR) for Treated Joint Bleeds
Timepoint [2] 0 0
From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks)
Secondary outcome [3] 0 0
Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
Timepoint [3] 0 0
From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks)
Secondary outcome [4] 0 0
Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds
Timepoint [4] 0 0
From Baseline to at least 24 weeks (median [min-max] efficacy periods for Arm C: 24.00 [14.4-25.0] weeks; Arm A: 29.57 [17.3-49.6] weeks; Arm B: 31.29 [3.3-50.6] weeks; Arm D: 33.14 [18.4-48.6] weeks)
Secondary outcome [5] 0 0
Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With Factor VIII (FVIII) Prophylaxis (NISP)
Timepoint [5] 0 0
Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks)
Secondary outcome [6] 0 0
Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With FVIII Prophylaxis (NISP)
Timepoint [6] 0 0
Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for Dnisp-FVIII Prophylaxis: 30.07 [5.0-45.1] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for Dnisp-Emicizumab Prophylaxis: 33.71 [20.1-48.6] weeks)
Secondary outcome [7] 0 0
Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE)
Timepoint [7] 0 0
Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks)
Secondary outcome [8] 0 0
Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE)
Timepoint [8] 0 0
Efficacy periods: At least 24 weeks prior to study entry (median [min-max] for A+Bnise-FVIII Episodic: 25.71 [15.4-40.9] weeks); and From Baseline to at least 24 weeks on study (median [min-max] for A+Bnise-Emicizumab: 34.71 [24.1-50.6] weeks)
Secondary outcome [9] 0 0
Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Subscore for Adult Participants (=18 Years of Age) in the Randomized Population at Week 25
Timepoint [9] 0 0
Baseline, Week 25
Secondary outcome [10] 0 0
Haem-A-QoL Questionnaire Total Score for Adult Participants (=18 Years of Age) in the Randomized Population at Week 25
Timepoint [10] 0 0
Baseline, Week 25
Secondary outcome [11] 0 0
European Quality of Life 5-Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score in the Randomized Population at Week 25
Timepoint [11] 0 0
Baseline, Week 25
Secondary outcome [12] 0 0
EQ-5D-5L Questionnaire Index Utility Score in the Randomized Population at Week 25
Timepoint [12] 0 0
Baseline, Week 25
Secondary outcome [13] 0 0
Hemophilia-Specific Quality of Life - Short Form (Haemo-QoL-SF) Questionnaire Score in Adolescent Participants (12 to 17 Years of Age) in the Randomized Population at Week 25
Timepoint [13] 0 0
Week 25
Secondary outcome [14] 0 0
Percentage of Participants With at Least One Adverse Event During the First 24 Weeks of the Study, Primary Analysis
Timepoint [14] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [15] 0 0
Percentage of Participants With at Least One Grade =3 Adverse Event During the First 24 Weeks of the Study, Primary Analysis
Timepoint [15] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [16] 0 0
Percentage of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment During the First 24 Weeks of the Study, Primary Analysis
Timepoint [16] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [17] 0 0
Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs During the First 24 Weeks of the Study, Primary Analysis
Timepoint [17] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [18] 0 0
Percentage of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings During the First 24 Weeks of the Study, Primary Analysis
Timepoint [18] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [19] 0 0
Percentage of Participants With at Least One Adverse Event of Abnormal Laboratory Values During the First 24 Weeks of the Study, Primary Analysis
Timepoint [19] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [20] 0 0
Percentage of Participants With at Least One Local Injection-Site Reaction During the First 24 Weeks of the Study, Primary Analysis
Timepoint [20] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [21] 0 0
Percentage of Participants With at Least One Thromboembolic Event During the First 24 Weeks of the Study, Primary Analysis
Timepoint [21] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [22] 0 0
Percentage of Participants With at Least One Thrombotic Microangiopathy During the First 24 Weeks of the Study, Primary Analysis
Timepoint [22] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [23] 0 0
Percentage of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction During the First 24 Weeks of the Study, Primary Analysis
Timepoint [23] 0 0
From Baseline to at least 24 weeks (median [min-max] safety periods for Arm C (Control): 24.00 [14.4-25.0] weeks; Arm A: 30.00 [21.4-49.6] weeks; Arm B: 31.29 [24.4-50.6] weeks; Arm C (Emi): 7.57 [0.3-26.3] weeks; Arm D: 33.71 [18.4-49.6] weeks)
Secondary outcome [24] 0 0
Safety Summary of the Percentage of Emicizumab-Treated Participants With at Least One Adverse Event During the Study
Timepoint [24] 0 0
From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks)
Secondary outcome [25] 0 0
Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants
Timepoint [25] 0 0
From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks)
Secondary outcome [26] 0 0
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants
Timepoint [26] 0 0
From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks)
Secondary outcome [27] 0 0
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds, All Emicizumab Participants
Timepoint [27] 0 0
From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 228.14 [7.3-288.3] weeks)
Secondary outcome [28] 0 0
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [28] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [29] 0 0
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [29] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [30] 0 0
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [30] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [31] 0 0
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [31] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [32] 0 0
Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [32] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [33] 0 0
Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time, All Emicizumab Participants
Timepoint [33] 0 0
1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, 253-264, 265-276, and 277-288 weeks
Secondary outcome [34] 0 0
Percentage of Participants With Anti-Emicizumab Antibodies at Any Time Post-Baseline During the Study
Timepoint [34] 0 0
From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks)
Secondary outcome [35] 0 0
Percentage of Participants With De Novo Development of Factor VIII (FVIII) Inhibitors
Timepoint [35] 0 0
From Baseline to discontinuation from study (median [min-max] observation period for all emicizumab participants: 262.3 [14.4-288.3] weeks)
Secondary outcome [36] 0 0
Trough Plasma Concentration (Ctrough) of Emicizumab
Timepoint [36] 0 0
Predose at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, 253, 265, and 277

Eligibility
Key inclusion criteria
- Body weight >/= 40 kilogram (kg) at the time of screening

- Diagnosis of severe congenital hemophilia A

- Documentation of the details of prophylactic or episodic FVIII treatment and of number
of bleeding episodes for at least the last 24 weeks

- Adequate hematologic function

- Adequate hepatic function

- Adequate renal function

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of less than (<) 1 percent (%) per year during the treatment period and for at least 5
elimination half-lives (24 weeks) after the last dose of study drug
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inherited or acquired bleeding disorder other than hemophilia A

- Previous or current treatment for thromboembolic disease or signs of thromboembolic
disease

- Conditions that may increase risk of bleeding or thrombosis

- History of clinically significant hypersensitivity associated with monoclonal antibody
therapies or components of the emicizumab injection

- Known human immunodeficiency virus (HIV) infection with cluster of differentiation
(CD) 4 count <200 cells per microliter (cells/mcL) within 24 weeks prior to screening.
Participants with HIV infection who has CD4 greater than (>) 200 and meet all other
criteria are eligible

- Use of systemic immunomodulators at enrollment or planned use during the study, with
the exception of anti-retroviral therapy

- Participants who are at high risk for thrombotic microangiopathy (TMA) (for example,
have a previous medical or family history of TMA), in the investigator's judgment

- Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
interfere with the conduct of the study, may pose additional risk, or would, in the
opinion of the investigator, preclude the participant's safe participation in and
completion of the study

- Planned surgery (excluding minor procedures) during the study

- Receipt of emicizumab in a prior investigational study; an investigational drug to
treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug
administration; a non-hemophilia-related investigational drug concurrently, within
last 30 days or 5 half-lives, whichever is shorter

- Pregnant or lactating, or intending to become pregnant during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
27/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/05/2022
Sample size
Target
Accrual to date
Final
152
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit - Melbourne
Recruitment hospital [3] 0 0
The Perth Blood Institute - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
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
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
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
Ireland
State/province [14] 0 0
Dublin
Country [15] 0 0
Italy
State/province [15] 0 0
Lombardia
Country [16] 0 0
Italy
State/province [16] 0 0
Toscana
Country [17] 0 0
Japan
State/province [17] 0 0
Aichi
Country [18] 0 0
Japan
State/province [18] 0 0
Kanagawa
Country [19] 0 0
Japan
State/province [19] 0 0
Miyagi
Country [20] 0 0
Japan
State/province [20] 0 0
Nara
Country [21] 0 0
Japan
State/province [21] 0 0
Osaka
Country [22] 0 0
Japan
State/province [22] 0 0
Tokyo
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Poland
State/province [24] 0 0
Gdansk
Country [25] 0 0
Poland
State/province [25] 0 0
Lublin
Country [26] 0 0
Poland
State/province [26] 0 0
Poznan
Country [27] 0 0
Poland
State/province [27] 0 0
Warsaw
Country [28] 0 0
South Africa
State/province [28] 0 0
Johannesburg
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Sevilla
Country [31] 0 0
Taiwan
State/province [31] 0 0
Chang Hua
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taichung
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taipei
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Cardiff
Country [35] 0 0
United Kingdom
State/province [35] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, global, multicenter, open-label, Phase 3 clinical study in participants
with severe hemophilia A without inhibitors against Factor VIII (FVIII) who are 12 years or
older. The study evaluates two prophylactic emicizumab regimens versus no prophylaxis in this
population with emphasis on efficacy, safety, and pharmacokinetics.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02847637
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
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries