A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors (HAVEN 2)

Roche

Status and phase: Completed; Phase 3

Conditions: Hemophilia A

Treatments: Drug: Emicizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02795767

2016-000073-21 (EudraCT Number)

BH29992

Details and patient eligibility

About

This non-randomized, multicenter, open-label, Phase III clinical study will evaluate the efficacy, safety, and pharmacokinetics of emicizumab administered subcutaneously initially once weekly (QW) in pediatric participants with hemophilia A with FVIII inhibitors. This study will open two additional non-randomized cohorts to investigate once every 2 weeks (Q2W) and once every 4 weeks (Q4W) regimens in pediatric participants.

Enrollment: 88 patients

Sex: All

Ages: Under 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children less than (<) 12 years of age, with allowance for participants 12 to 17 years of age who weigh <40 kilograms (kg) (Cohort A only); and participants <2 years of age will be allowed to participate only after the protocol-defined interim data review criteria are met (Cohort A only)
• Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (that is [i.e.], greater than or equal to [>/=] 5 bethesda units [BU])
• Requires treatment with bypassing agents
• Adequate hematologic, hepatic, and renal function

Exclusion criteria

• Inherited or acquired bleeding disorder other than hemophilia A
• Ongoing (or planning to receive during the study) immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII
• Previous (in the past 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
• Other disease that may increase risk of bleeding or thrombosis
• History of clinically significant hypersensitivity associated with monoclonal antibody therapy or components of the emicizumab injection
• Known infection with human immunodeficiency virus (HIV) or hepatitis B or C virus
• Use of systemic immunomodulators at enrollment or planned use during the study period
• Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
• Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition)
• Participants who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator's judgement

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

88 participants in 3 patient groups

Cohort A: 1.5 mg/kg Emicizumab QW

Experimental group

Description:

Participants will receive emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Treatment:

Drug: Emicizumab

Cohort B: 3 mg/kg Emicizumab Q2W

Experimental group

Description:

Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 3 mg/kg every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Treatment:

Drug: Emicizumab

Cohort C: 6 mg/kg Emicizumab Q4W

Experimental group

Description:

Participants will receive emicizumab at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 6 mg/kg every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurs first.

Treatment:

Drug: Emicizumab