A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Condition: Hemophilia A
MeSH terms: Hemophilia A
Intervention: Emicizumab
Intervention description: Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 195.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and
      tolerability of emicizumab in participants with congenital hemophilia A who have documented
      inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12
      or older, will be enrolled in this study and are expected to be enrolled at approximately 85
      sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab
      subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the
      remainder of the 2-year treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  As per investigator's judgement, a willingness and ability to comply with scheduled
             visits, treatment plans, laboratory tests, and other study procedures, including the
             patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an
             electronic device or paper

          -  Aged 12 years or older at the time of informed consent

          -  Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII

          -  Documented treatment with bypassing agents or FVIII concentrates in the last 6 months
             (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day
             before starting emicizumab

          -  Adequate hematologic, hepatic, and renal function

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use a highly effective contraceptive method with a
             failure rate of <1% per year during the treatment period and for at least five
             elimination half-lives (24 weeks) after the last dose of emicizumab

        Exclusion Criteria:

          -  Inherited or acquired bleeding disorder other than hemophilia A

          -  Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy
             (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to
             enrollment). Patients receiving ITI therapy will be eligible following the completion
             of a 72-hour washout period prior to the first emicizumab administration

          -  History of illicit drug or alcohol abuse within 12 months prior to screening, as per
             the investigator's judgment

          -  High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or
             family history of TMA), as per the investigator's judgment

          -  Previous (in the past 12 months) or current treatment for thromboembolic disease (with
             the exception of previous catheter-associated thrombosis for which antithrombotic
             treatment is not currently ongoing) or current signs of thromboembolic disease

          -  Other conditions (e.g., certain autoimmune diseases) that may increase the risk of
             bleeding or thrombosis

          -  History of clinically significant hypersensitivity reaction associated with monoclonal
             antibody therapies or components of the emicizumab injection

          -  Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/μL within
             6 months prior to screening

          -  Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or
             planned use during the study, with the exception of antiretroviral therapy

          -  Concurrent disease, treatment, or abnormality in clinical laboratory tests that could
             interfere with the conduct of the study or that would, in the opinion of the
             investigator or Sponsor, preclude the patient's safe participation in and completion
             of the study or interpretation of the study results

          -  Receipt of: Emicizumab in a prior investigational study; An investigational drug to
             treat or reduce the risk of hemophilic bleeds within five half-lives of last drug
             administration; A non-hemophilia-related investigational drug within last 30 days or
             five half-lives, whichever is shorter; or, Any concurrent investigational drug.

          -  Pregnancy or lactation, or intent to become pregnant during the study

          -  Positive serum pregnancy test result within 7 days prior to initiation of emicizumab
             (females only)