A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Emicizumab in Participants With Mild or Moderate Hemophilia A Without FVIII Inhibitors
Condition: Mild Hereditary Factor VIII Deficiency Disease Without Inhibitor; Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor; Hemophilia A
MeSH terms: Hemophilia A; Deficiency Diseases
Intervention: Emicizumab
Intervention description: Four loading doses of emicizumab 3 milligrams per kilogram of body weight (mg/kg) will be administered subcutaneously (SC) once a week (QW) for 4 weeks followed by participant's preference of one of the three following maintenance SC dose regimens: 1.5 mg/kg QW, 3 mg/kg once every 2 weeks (Q2W), or 6 mg/kg once every 4 weeks (Q4W).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Healthy volunteers: No
Keywords: Mild Hemophilia A Without Factor VIII Inhibitors; Moderate Hemophilia A Without Factor VIII Inhibitors

Summary:

      This is a multicenter, open-label, single-arm study designed to evaluate the safety,
      efficacy, pharmacokinetics, and pharmacodynamics of emicizumab in participants with mild or
      moderate hemophilia A without inhibitors against factor VIII (FVIII).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of mild (FVIII level between >5% and <40%) or moderate (FVIII level between
             ≥1% and ≤5%) congenital Hemophilia A without FVIII inhibitors

          -  Weight ≥3 kilograms (kg)

          -  Need for prophylaxis based on investigator assessment

          -  A negative test for inhibitor (i.e., <0.6 Bethesda Units per milliliter [BU/mL])
             within 8 weeks prior to enrollment

          -  No documented inhibitor (i.e., <0.6 BU/mL), FVIII half-life <6 hours, or FVIII
             recovery <66% in the last 5 years

          -  Documentation of the details of prophylactic or episodic FVIII treatment and of number
             of bleeding episodes for at least the last 24 weeks prior to enrollment

          -  Adequate hematologic, hepatic, and renal function

          -  For women of childbearing potential: agreement to remain abstinent or use
             contraception (as defined in the protocol) during the treatment period and for at
             least 24 weeks after the final dose of study drug

        Exclusion Criteria:

          -  Inherited or acquired bleeding disorder other than mild or moderate congenital
             hemophilia A

          -  History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the
             investigator's judgment

          -  Previous (within the last 12 months) or current treatment for thromboembolic disease
             or signs of thromboembolic disease

          -  Other conditions 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

          -  Planned surgery during the emicizumab loading dose phase (surgeries in participants on
             emicizumab from Week 5 onwards are allowed)

          -  Known HIV infection with CD4 counts <200 cells per microlitre (/μL)

          -  Concomitant disease, condition, significant abnormality on screening evaluation 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

          -  Receipt of any of the following: An investigational drug to treat or reduce the risk
             of hemophilic bleeds within 5 half-lives of last drug administration with the
             exception of prior emicizumab prophylaxis; A non-hemophilia-related investigational
             drug within last 30 days or 5 half-lives, whichever is shorter; or Any other
             investigational drug currently being administered or planned to be administered

          -  Inability to comply with the study protocol in the opinion of the investigator

          -  Pregnant or breastfeeding, or intending to become pregnant during the study (women of
             childbearing potential must have a negative serum pregnancy test result within 7 days
             prior to initiation of study drug)