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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/NCT04431726
Registration number
NCT04431726
Ethics application status
Date submitted
11/06/2020
Date registered
16/06/2020
Date last updated
13/02/2024
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
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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
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Secondary ID [1]
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2020-001733-12
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Secondary ID [2]
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MO41787
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Universal Trial Number (UTN)
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Trial acronym
HAVEN 7
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Severe Hemophilia A
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Condition category
Condition code
Blood
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Clotting disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Model-Based Annualized Bleeding Rate for Treated Bleeds
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Assessment method [1]
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Timepoint [1]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [2]
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Median Calculated Annualized Bleeding Rate for Treated Bleeds
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Assessment method [2]
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Timepoint [2]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [3]
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Mean Calculated Annualized Bleeding Rate for Treated Bleeds
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Assessment method [3]
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Timepoint [3]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [4]
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Model-Based Annualized Bleeding Rate for All Bleeds
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Assessment method [4]
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Timepoint [4]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [5]
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Median Calculated Annualized Bleeding Rate for All Bleeds
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Assessment method [5]
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Timepoint [5]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [6]
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Mean Calculated Annualized Bleeding Rate for All Bleeds
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Assessment method [6]
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Timepoint [6]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [7]
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Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
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Assessment method [7]
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Timepoint [7]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [8]
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Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
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Assessment method [8]
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Timepoint [8]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [9]
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Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
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Assessment method [9]
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Timepoint [9]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [10]
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Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
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Assessment method [10]
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Timepoint [10]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [11]
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Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
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Assessment method [11]
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Timepoint [11]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Primary outcome [12]
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Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
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Assessment method [12]
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Timepoint [12]
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From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
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Secondary outcome [1]
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Hemophilia Joint Health Score (HJHS) Total Score at Specified Timepoints During the Long-Term Follow-Up Period
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Assessment method [1]
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Timepoint [1]
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At 4, 5, 6, 7, and 8 years
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Secondary outcome [2]
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Magnetic Resonance Imaging (MRI) Score of Specific Joints at Specified Timepoints During the Long-Term Follow-Up Period
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Assessment method [2]
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Timepoint [2]
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At 5 and 8 years
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Secondary outcome [3]
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Incidence and Severity of Adverse Events, with Severity Determined According to World Health Organization (WHO) Toxicity Grading Scale
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Assessment method [3]
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Timepoint [3]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [4]
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Incidence of Thromboembolic Events
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Assessment method [4]
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Timepoint [4]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [5]
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Incidence of Thrombotic Microangiopathy
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Assessment method [5]
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Timepoint [5]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [6]
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Incidence and Severity of of Injection Site Reactions, with Severity Determined According to WHO Toxicity Grading Scale
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Assessment method [6]
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Timepoint [6]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [7]
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Incidence of Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Events
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Assessment method [7]
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0
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Timepoint [7]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [8]
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Incidence of Adverse Events Leading to Study Drug Discontinuation
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Assessment method [8]
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Timepoint [8]
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From Baseline until study completion (up to 8 years)
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Secondary outcome [9]
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Incidence of Laboratory Abnormalities in Serum Chemistry and Hematology Tests
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Assessment method [9]
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Timepoint [9]
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Baseline, Weeks 4, 13, 21, 29, 37, 45, and 53
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Secondary outcome [10]
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Change from Baseline in Pulse Rate Over Time
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Assessment method [10]
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Timepoint [10]
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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)
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Secondary outcome [11]
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Change from Baseline in Respiratory Rate Over Time
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Assessment method [11]
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Timepoint [11]
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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)
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Secondary outcome [12]
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Change from Baseline in Body Temperature Over Time
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Assessment method [12]
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Timepoint [12]
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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)
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Secondary outcome [13]
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Change from Baseline in Systolic Blood Pressure Over Time
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Assessment method [13]
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Timepoint [13]
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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)
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Secondary outcome [14]
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Change from Baseline in Diastolic Blood Pressure Over Time
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Assessment method [14]
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Timepoint [14]
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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)
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Secondary outcome [15]
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Plasma Trough Concentrations (Ctrough) of Emicizumab
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Assessment method [15]
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Timepoint [15]
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Predose at Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
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Secondary outcome [16]
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Incidence of Anti-Emicizumab Antibodies
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Assessment method [16]
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Timepoint [16]
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Weeks 1, 5, 17, 29, 41, and 53, and thereafter as clinically indicated until study completion (up to 8 years)
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Secondary outcome [17]
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Incidence of De Novo Development of Factor VIII Inhibitors
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Assessment method [17]
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Timepoint [17]
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As clinically indicated from baseline until study completion (up to 8 years)
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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
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Minimum age
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Months
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Maximum age
12
Months
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/02/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
20/05/2030
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Actual
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Sample size
Target
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Accrual to date
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Final
55
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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The Children's Hospital at Westmead - Westmead
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Recruitment hospital [2]
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Royal Children's Hospital - Parkville
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Recruitment hospital [3]
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Perth Children's Hospital - Nedlands
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment postcode(s) [2]
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3052 - Parkville
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arizona
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Country [2]
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United States of America
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State/province [2]
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California
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Country [3]
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0
United States of America
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State/province [3]
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Colorado
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Country [4]
0
0
United States of America
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State/province [4]
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Louisiana
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Michigan
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Country [6]
0
0
United States of America
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State/province [6]
0
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Washington
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Country [7]
0
0
Austria
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State/province [7]
0
0
Wien
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Country [8]
0
0
Belgium
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State/province [8]
0
0
Bruxelles
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Country [9]
0
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Belgium
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State/province [9]
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Leuven
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Country [10]
0
0
Brazil
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State/province [10]
0
0
SP
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Country [11]
0
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Canada
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State/province [11]
0
0
Ontario
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Country [12]
0
0
France
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State/province [12]
0
0
Paris
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Country [13]
0
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Germany
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State/province [13]
0
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Bonn
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Country [14]
0
0
Germany
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State/province [14]
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0
Mörfelden-Walldorf
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Country [15]
0
0
Israel
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State/province [15]
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0
Tel Hashomer
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Country [16]
0
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Italy
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State/province [16]
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0
Campania
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Country [17]
0
0
Italy
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State/province [17]
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Emilia-Romagna
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Country [18]
0
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Italy
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State/province [18]
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Lombardia
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Country [19]
0
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Italy
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State/province [19]
0
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Toscana
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Country [20]
0
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South Africa
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State/province [20]
0
0
Johannesburg
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Country [21]
0
0
Spain
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State/province [21]
0
0
Barcelona
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Country [22]
0
0
Spain
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State/province [22]
0
0
Madrid
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Country [23]
0
0
Spain
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State/province [23]
0
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Sevilla
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Country [24]
0
0
Turkey
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State/province [24]
0
0
Adana
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Country [25]
0
0
Turkey
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State/province [25]
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0
Ankara
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Country [26]
0
0
Turkey
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State/province [26]
0
0
Izmir
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Country [27]
0
0
Turkey
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State/province [27]
0
0
Samsun
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Country [28]
0
0
United Kingdom
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State/province [28]
0
0
Cardiff
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Country [29]
0
0
United Kingdom
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State/province [29]
0
0
Glasgow
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Country [30]
0
0
United Kingdom
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State/province [30]
0
0
London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a Phase IIIb, multicenter, open-label, single-arm study of prophylactic emicizumab in
previously untreated and minimally treated patients at study enrollment from birth to =12
months of age with severe hemophilia A (intrinsic factor VIII [FVIII] level <1%) without
FVIII inhibitors. The study is designed to evaluate the efficacy, safety, pharmacokinetics,
and pharmacodynamics of emicizumab administered at 3 milligrams per kilogram of body weight
(mg/kg) once every 2 weeks (Q2W) for 52 weeks. After 1 year of treatment, participants will
continue to receive emicizumab (1.5 mg/kg once every week [QW], 3 mg/kg Q2W or 6 mg/kg once
every 4 weeks [Q4W]) over a 7-year long-term follow-up period under this study frame.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04431726
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
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0
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Email
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0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04431726
Download to PDF