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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04431726




Registration number
NCT04431726
Ethics application status
Date submitted
11/06/2020
Date registered
16/06/2020

Titles & IDs
Public title
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Participants From Birth to 12 Months of Age With Hemophilia A Without Inhibitors
Scientific title
A Phase IIIb, Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients From Birth to 12 Months of Age With Hemophilia A Without Inhibitors
Secondary ID [1] 0 0
2020-001733-12
Secondary ID [2] 0 0
MO41787
Universal Trial Number (UTN)
Trial acronym
HAVEN 7
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe 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

Experimental: Emicizumab -


Treatment: Drugs: Emicizumab
Initially, all participants will receive 4 loading doses of 3 milligrams per kilogram (mg/kg) emicizumab subcutaneously (SC) once every week (QW) for 4 weeks followed by the maintenance dosing regimen 3 mg/kg emicizumab SC once every 2 weeks (Q2W) for a total of 52 weeks. Starting from Week 17 of treatment, individual participants may have their dose up-titrated to 3 mg/kg SC QW if they experience suboptimal bleeding control.

At the Week 53 clinic visit following consultation with the treating physician, parents/caregivers may elect for their child to continue with the maintenance 3-mg/kg SC Q2W dosing regimen or to switch to the maintenance 1.5-mg/kg SC QW or 6-mg/kg SC once every 4 weeks (Q4W) dosing regimen for the subsequent 7-year long-term follow-up period.

During the study, participants will be treated with emicizumab until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria specified in the protocol, whichever occurs first.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Model-Based Annualized Bleeding Rate for Treated Bleeds
Timepoint [1] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [2] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Bleeds
Timepoint [2] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [3] 0 0
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Timepoint [3] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [4] 0 0
Model-Based Annualized Bleeding Rate for All Bleeds
Timepoint [4] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [5] 0 0
Mean Calculated Annualized Bleeding Rate for All Bleeds
Timepoint [5] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [6] 0 0
Median Calculated Annualized Bleeding Rate for All Bleeds
Timepoint [6] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [7] 0 0
Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [7] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [8] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [8] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [9] 0 0
Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Timepoint [9] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [10] 0 0
Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [10] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [11] 0 0
Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [11] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Primary outcome [12] 0 0
Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Timepoint [12] 0 0
From first dose of emicizumab to the clinical cutoff date or withdrawal date, whichever was earlier (median [range, min-max] efficacy period: 101.9 [52.6-119.7] weeks)
Secondary outcome [1] 0 0
Hemophilia Joint Health Score (HJHS) Total Score at Specified Timepoints During the Long-Term Follow-Up Period
Timepoint [1] 0 0
At Years 4, 5, 6, 7, and 8 of follow-up
Secondary outcome [2] 0 0
Magnetic Resonance Imaging (MRI) Score of Specific Joints at Specified Timepoints During the Long-Term Follow-Up Period
Timepoint [2] 0 0
At Years 5 and 8 of follow-up
Secondary outcome [3] 0 0
Incidence and Severity of Adverse Events, With Severity Determined According to World Health Organization (WHO) Toxicity Grading Scale
Timepoint [3] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [4] 0 0
Incidence of Thromboembolic Events
Timepoint [4] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [5] 0 0
Incidence of Thrombotic Microangiopathy
Timepoint [5] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [6] 0 0
Incidence and Severity of of Injection Site Reactions, With Severity Determined According to WHO Toxicity Grading Scale
Timepoint [6] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [7] 0 0
Incidence of Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Events
Timepoint [7] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [8] 0 0
Incidence of Adverse Events Leading to Study Drug Discontinuation
Timepoint [8] 0 0
From first dose of emicizumab until study completion (8 years)
Secondary outcome [9] 0 0
Number of Participants According to Hematology and Serum Chemistry Laboratory Test Result Shifts From Baseline WHO Grade to the Highest WHO Grade Post-Baseline
Timepoint [9] 0 0
Baseline, Weeks 4, 13, 21, 29, 37, 45, and 53
Secondary outcome [10] 0 0
Change From Baseline in Pulse Rate Over Time
Timepoint [10] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
Secondary outcome [11] 0 0
Change From Baseline in Respiratory Rate Over Time
Timepoint [11] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
Secondary outcome [12] 0 0
Change From Baseline in Body Temperature Over Time
Timepoint [12] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
Secondary outcome [13] 0 0
Change From Baseline in Systolic Blood Pressure Over Time
Timepoint [13] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
Secondary outcome [14] 0 0
Change From Baseline in Diastolic Blood Pressure Over Time
Timepoint [14] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
Secondary outcome [15] 0 0
Plasma Trough Concentrations (Ctrough) of Emicizumab
Timepoint [15] 0 0
Predose at Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
Secondary outcome [16] 0 0
Incidence of Anti-Emicizumab Antibodies
Timepoint [16] 0 0
Weeks 1, 5, 17, 29, 41, and 53, and thereafter as clinically indicated until study completion (up to 8 years)
Secondary outcome [17] 0 0
Incidence of De Novo Development of Factor VIII Inhibitors
Timepoint [17] 0 0
As clinically indicated from baseline until study completion (up to 8 years)

Eligibility
Key inclusion criteria
* Age from birth to =12 months at time of informed consent
* Body weight =3 kilograms (kg) at time of informed consent. Patients with a lower body weight can be enrolled after they have reached a body weight of 3 kg. Premature babies (gestational age <38 weeks) may be enrolled as long as they have reached a body weight of 3 kg. For premature babies, the corrected gestational age should be reported.
* Mandatory receipt of vitamin K prophylaxis according to local standard practice
* Diagnosis of severe congenital hemophilia A (intrinsic FVIII level <1%)
* A negative test for FVIII inhibitor (i.e., <0.6 Bethesda units [BU]/mL) locally assessed during the 2-week screening period
* No history of documented FVIII inhibitor (i.e., <0.6 BU/mL), FVIII drug-elimination half-life <6 hours, or FVIII recovery <66%
* Previously untreated patients or minimally treated patients (i.e., up to 5 days of exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)
* Documentation of the details of the hemophilia-related treatments received since birth
* Documentation of the details of the bleeding episodes since birth
* For patients from birth to <3 months of age at the time of study entry: no evidence of active intracranial hemorrhage, as confirmed by a negative cranial ultrasound at screening irrespective of delivery mode
* Adequate hematologic, hepatic, and renal function, as defined in the protocol
* For parents/caregivers: willingness and ability to comply with the study protocol requirements, scheduled visits, treatment plans, laboratory tests, completion of applicable questionnaires, and other study procedures
Minimum age
0 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inherited or acquired bleeding disorder other than severe hemophilia A
* Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study
* Receipt of any of the following: Prior use of emicizumab prophylaxis including investigational or commercial emicizumab; An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 drug-elimination half-lives of last drug administration; A non-hemophilia-related investigational drug within the last 30 days or 5 drug-elimination half-lives, whichever is shorter; An investigational drug concurrently
* Current active severe bleed, such as intracranial hemorrhage
* Planned surgery (excluding minor procedures, e.g., circumcision, CVAD placement) during the study
* History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
* Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA, such as thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome) in the investigator's judgment
* Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis in patients for whom anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
* Any hereditary or acquired maternal condition that may predispose the patient to thrombotic events (e.g., inherited thrombophilias antiphospholipid syndrome)
* Other diseases (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
* Known infection with HIV, hepatitis B virus, or hepatitis C virus
* Serious infection requiring antibiotics or antiviral treatments within 14 days prior to screening
* Concurrent disease, treatment, abnormality in clinical laboratory tests, vital signs measurements, or physical examination findings that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
* Unwillingness of the parent or caregiver to allow receipt of blood or blood products, or any standard-of-care treatment for a life-threatening condition
* Any other medical, social, or other condition that may prevent adequate compliance with the study protocol in the opinion of the investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
20/05/2030
Actual
Sample size
Target
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
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
Washington
Country [7] 0 0
Austria
State/province [7] 0 0
Wien
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Brazil
State/province [10] 0 0
SP
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
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
Germany
State/province [14] 0 0
Mörfelden-Walldorf
Country [15] 0 0
Israel
State/province [15] 0 0
Tel Hashomer
Country [16] 0 0
Italy
State/province [16] 0 0
Campania
Country [17] 0 0
Italy
State/province [17] 0 0
Emilia-Romagna
Country [18] 0 0
Italy
State/province [18] 0 0
Lombardia
Country [19] 0 0
Italy
State/province [19] 0 0
Toscana
Country [20] 0 0
South Africa
State/province [20] 0 0
Johannesburg
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Sevilla
Country [24] 0 0
Turkey
State/province [24] 0 0
Adana
Country [25] 0 0
Turkey
State/province [25] 0 0
Ankara
Country [26] 0 0
Turkey
State/province [26] 0 0
Izmir
Country [27] 0 0
Turkey
State/province [27] 0 0
Samsun
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Cardiff
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Glasgow
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

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
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


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/NCT04431726