A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Emicizumab; Factor VIII (FVIII)
Intervention description: Participants received emicizumab prophylaxis subcutaneously at the specified dose for each arm. 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 4 (20-Dec-2019), treatment duration was extended. During this study prolongation, each participant had the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg once every 4 weeks [Q4W]) and continue on that dosing regimen until discontinuation from the study.; FVIII was allowed to treat bleeds on an episodic basis, per the local prescribing information. Specific dosages of FVIII were not mandated in the study. Breakthrough bleeds were to be treated with the lowest FVIII dose expected to achieve hemostasis, which may have been lower than the participant's prior FVIII dose. To avoid bleeds before adequate emicizumab level is reached, patients in Arm D continued their regular FVIII prophylaxis until the second emicizumab loading dose. Concomitant routine FVIII prophylaxis was not permissible otherwise during the study.
Intervention MeSH terms: Factor VIII
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 152.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Hemophilia A; Emicizumab

Summary:

      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.
    

Eligibility criteria:

        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