A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks in Participants With Hemophilia A
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Emicizumab
Intervention description: Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      This multicenter, open-label, non-randomized study will assess the efficacy, safety,
      pharmacokinetics, and pharmacodynamics of emicizumab administered at a dose of 6 milligrams
      per kilogram (mg/kg) every 4 weeks in participants with hemophilia A with or without
      inhibitors against factor VIII (FVIII). The study consists of 2 parts: a pharmacokinetic (PK)
      run-in part followed by an expansion part.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body weight greater than or equal to (>/=) 40 kilograms (kg) at screening

          -  Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors

          -  Participants using rFVIIa or willing to switch to recombinant activated factor VII
             (rFVIIa) as primary bypassing agent for the treatment of breakthrough bleeds

          -  FVIII inhibitor test during screening with titer results available prior to first
             administration of study drug

          -  Participants without FVIII inhibitors, that is with less than (<) 0.6 Bethesda unit
             per milliliter [BU/mL];< 1.0 BU/mL only for laboratories with an historical
             sensitivity cutoff for inhibitor detection of 1.0 BU/mL, who completed successful
             immune tolerance induction (ITI) must have done so at least 5 years before screening
             and must have no evidence of inhibitor recurrence (permanent or temporary) indicated
             by detection of an inhibitor greater than (>) 0.6 BU/mL (> 1.0 BU/mL only for
             laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0
             BU/mL) since ITI

          -  Adequate hematologic, hepatic, and renal function

        Exclusion Criteria:

          -  Inherited or acquired bleeding disorder other than hemophilia A

          -  Ongoing or planned ITI therapy; participants in whom ITI has failed will be eligible
             with a 72-hour washout period prior to the first emicizumab administration

          -  History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the
             investigator's judgment

          -  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

          -  Previous (within the last 12 months) or current treatment for thromboembolic disease
             (with the exception of previous catheter-associated thrombosis for which
             anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease

          -  Other conditions (for example, certain autoimmune diseases) that may currently
             increase the risk of bleeding or thrombosis

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known HIV infection with cluster of differentiation (CD) 4 cells counts <200 cells per
             microliter (cells/mcL)

          -  Use of systemic immunomodulators (for example, interferon) at enrollment or planned
             use during the study, with the exception of anti-retroviral therapy

          -  Concomitant disease, condition, significant abnormality on screening evaluations or
             laboratory tests, or treatment that could interfere with the conduct of the study, or
             that would, in the opinion of the investigator, pose an additional unacceptable risk
             in administering study drug to the participant

          -  Pregnancy or lactation or intention to become pregnant during the study

          -  Women with a positive serum pregnancy test result within 7 days prior to initiation of
             study drug