A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors (HAVEN 3)
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ClinicalTrials.gov Identifier: NCT02847637 |
Recruitment Status :
Completed
First Posted : July 28, 2016
Results First Posted : November 14, 2018
Last Update Posted : November 16, 2022
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Sponsor:
Hoffmann-La Roche
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche
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Study Type | Interventional |
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Study Design | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Hemophilia A |
Interventions |
Drug: Emicizumab Drug: Factor VIII (FVIII) |
Enrollment | 152 |
Participant Flow
Recruitment Details | |
Pre-assignment Details | A total of 161 participants were screened; 9 failed screening, and 152 participants, who had previously received either episodic or prophylactic treatment with FVIII agents, were enrolled in this study. Participants in Arms C, A, and B were randomized in a 1:2:2 ratio, respectively; participants in Arm D were enrolled without randomization. |
Arm/Group Title | Arm C (Control): No Prophylaxis, Then Emicizumab | Arm A: Emicizumab 1.5 mg/kg QW | Arm B: Emicizumab 3 mg/kg Q2W | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) |
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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 milligrams per kilogram (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. | 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. | 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 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. | 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. |
Period Title: Overall Study | ||||
Started | 18 | 36 | 35 | 63 |
Completed First 24 Weeks of Treatment | 16 [1] | 35 | 34 | 63 |
Emicizumab Dose Was Up-Titrated | 0 | 1 | 1 | 7 |
Opted to Change Emicizumab Dosing Regimen [2] | 1 | 3 | 1 | 1 |
Completed | 17 | 34 | 34 | 63 |
Not Completed | 1 | 2 | 1 | 0 |
Reason Not Completed | ||||
Withdrawal by Subject | 0 | 1 | 1 | 0 |
Lost to Follow-up | 1 | 1 | 0 | 0 |
[1]
A total of 17 participants in Arm C switched from no prophylaxis to receive emicizumab prophylaxis; however, 1 switched to emicizumab prior to completing 24 weeks on no prophylaxis (at 23.5 weeks).
[2]
Upon Implementation of Protocol Version 4
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Baseline Characteristics
Arm/Group Title | Arm C (Control): No Prophylaxis, Then Emicizumab | Arm A: Emicizumab 1.5 mg/kg QW | Arm B: Emicizumab 3 mg/kg Q2W | Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis) | Total | |
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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 milligrams per kilogram (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. | 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. | 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 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. | 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. | Total of all reporting groups | |
Overall Number of Baseline Participants | 18 | 36 | 35 | 63 | 152 | |
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[Not Specified]
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
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Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants | |
37.8 (12.9) | 39.8 (14.0) | 40.4 (11.4) | 36.4 (14.4) | 38.3 (13.5) | ||
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants | |
Female |
0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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Male |
18 100.0%
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36 100.0%
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35 100.0%
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63 100.0%
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152 100.0%
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Ethnicity (NIH/OMB)
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants | |
Hispanic or Latino |
0 0.0%
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4 11.1%
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5 14.3%
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7 11.1%
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16 10.5%
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Not Hispanic or Latino |
17 94.4%
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32 88.9%
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30 85.7%
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53 84.1%
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132 86.8%
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Unknown or Not Reported |
1 5.6%
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0 0.0%
|
0 0.0%
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3 4.8%
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4 2.6%
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Race (NIH/OMB)
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants | |
American Indian or Alaska Native |
0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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Asian |
4 22.2%
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6 16.7%
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10 28.6%
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12 19.0%
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32 21.1%
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Native Hawaiian or Other Pacific Islander |
0 0.0%
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1 2.8%
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0 0.0%
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0 0.0%
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1 0.7%
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Black or African American |
3 16.7%
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3 8.3%
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1 2.9%
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1 1.6%
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8 5.3%
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White |
11 61.1%
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24 66.7%
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20 57.1%
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47 74.6%
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102 67.1%
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More than one race |
0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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0 0.0%
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Unknown or Not Reported |
0 0.0%
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2 5.6%
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4 11.4%
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3 4.8%
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9 5.9%
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Number of Participants with <9 or ≥9 Bleeds in the Last 24 Weeks Prior to Study Entry
Measure Type: Count of Participants Unit of measure: Participants |
Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants |
Less Than (<) 9 Bleeds |
4 22.2%
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9 25.0%
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5 14.3%
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53 84.1%
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71 46.7%
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Greater Than or Equal To (≥) 9 Bleeds |
14 77.8%
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27 75.0%
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30 85.7%
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10 15.9%
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81 53.3%
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Number of Target Joints in the Last 24 Weeks Prior to Study Entry
[1] Mean (Standard Deviation) Unit of measure: Target joints |
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Number Analyzed | 18 participants | 36 participants | 35 participants | 63 participants | 152 participants | |
2.2 (1.4) | 2.1 (1.4) | 2.2 (1.7) | 1.0 (1.6) | 1.7 (1.6) | ||
[1]
Measure Description: A target joint was defined as at least 3 bleeds into the same joint over the last 24 weeks prior to study entry.
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Outcome Measures
Adverse Events