A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors (HAVEN 3)

Roche

Status and phase: Completed; Phase 3

Conditions: Hemophilia A

Treatments: Drug: Factor VIII (FVIII); Drug: Emicizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02847637

BH30071

2016-000072-17 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 152 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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152 participants in 4 patient groups

Arm C (Control): No Prophylaxis, Then Emicizumab

Active Comparator group

Description:

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.

Treatment:

Drug: Factor VIII (FVIII)

Drug: Emicizumab

Arm A: Emicizumab 1.5 mg/kg QW

Experimental group

Description:

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.

Treatment:

Drug: Factor VIII (FVIII)

Drug: Emicizumab

Arm B: Emicizumab 3 mg/kg Q2W

Experimental group

Description:

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.

Treatment:

Drug: Factor VIII (FVIII)

Drug: Emicizumab

Arm D: Emicizumab 1.5 mg/kg QW (Pre-study FVIII Prophylaxis)

Experimental group

Description:

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:

Drug: Factor VIII (FVIII)

Drug: Emicizumab