A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
Condition: Hemophilia
MeSH terms: Hemophilia A
Intervention: Fitusiran; BPA prophylaxis; Factor (FVIII or FIX) prophylaxis
Intervention description: Pharmaceutical form: solution for injection Route of administration: subcutaneous; Pharmaceutical form: solution for injection Route of administration: Intravenous; Pharmaceutical form: solution for injection Route of administration: Intravenous
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: Male
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To characterize the frequency of bleeding episodes (BE) while receiving fitusiran treatment,
      relative to the frequency of bleeding episodes while receiving factor concentrate or
      bypassing agent (BPA) prophylaxis.

      Secondary Objectives:

        -  To characterize the following while receiving fitusiran treatment, relative to receiving
           factor or BPA prophylaxis:

        -  the frequency of spontaneous bleeding episodes

        -  the frequency of joint bleeding episodes

        -  health related quality of life (HRQOL) in participants greater than or equal to (>=) 17
           years of age

        -  To characterize the frequency of bleeding episodes during the onset and treatment
           periods in participants receiving fitusiran.

        -  To characterize the safety and tolerability of fitusiran.

        -  To characterize the annualized weight-adjusted consumption of factor/BPA while receiving
           fitusiran treatment, relative to receiving factor or BPA prophylaxis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males, >=12 years of age.

          -  Severe hemophilia A or B (as evidenced by a central laboratory measurement at
             screening or documented medical record evidence of FVIII less than (<) 1 percent (%)
             or FIX level less than or equal to (<=) 2%).

          -  A minimum of 2 bleeding episodes required BPA treatment within the last 6 months prior
             to screening for participants with inhibitory antibodies to factor VIII or factor IX
             (Cohort A). A minimum of 1 bleeding episode required factor treatment within the last
             12 months prior to screening for participants without inhibitory antibodies to factor
             VIII or factor IX (Cohort B).

          -  Met either the definition of inhibitor or non-inhibitor participant as below:

          -  Inhibitor: Use of BPAs for prophylaxis and for any bleeding episodes for at least the
             last 6 months prior to screening, and met one of the following Nijmegen-modified
             Bethesda assay results criteria:

          -  Inhibitor titer of >=0.6 Bethesda Unit per milliliter (BU/mL) at screening, or

          -  Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of 2
             consecutive titers >=0.6 BU/mL, or

          -  Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of anamnestic
             response

          -  The subgroup of participants in Cohort A participants might additionally meet the
             following criteria to be eligible to start treatment with fitusiran directly after the
             screening period:

               -  Hemophilia B with inhibitory antibody to Factor IX as defined above

               -  Not responding adequately to BPA treatment (historical ABR >=20) prior to
                  enrollment

               -  In the opinion of the Investigator, with approval of Sponsor Medical Monitor,
                  6-month BPA prophylaxis period should be omitted.

          -  Non-inhibitor: Use of factor concentrates for prophylaxis and for any bleeding
             episodes for at least the last 6 months prior to screening, and met each of the
             following criterion:

          -  Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at screening and

          -  No use of BPAs to treat bleeding episodes for at least the last 6 months prior to
             screening and

          -  No history of immune tolerance induction therapy within the past 3 years prior to
             screening.

          -  Documented prophylactic treatment with factor concentrates or BPAs for the treatment
             of hemophilia A or B for at least 6 months prior to screening.

          -  Adherent to the prescribed prophylactic therapy for at least 6 months prior to
             screening per Investigator assessment.

          -  Willed and complied with the study requirements and to provide written informed
             consent and assent.

        Exclusion Criteria:

          -  Known co-existing bleeding disorders other than hemophilia A or B.

          -  AT activity <60% at screening.

          -  Co-existing thrombophilic disorder.

          -  Clinically significant liver disease.

          -  Active Hepatitis C virus infection.

          -  Acute or chronic Hepatitis B virus infection.

          -  HIV positive with a CD4 count of <200 cells per microliter.

          -  History of arterial or venous thromboembolism.

          -  Inadequate renal function.

          -  History of multiple drug allergies or history of allergic reaction to an
             oligonucleotide or N-Acetylgalactosamine (GalNAc).

          -  History of intolerance to subcutaneous injection(s).

          -  Any other conditions or comorbidities that made the participant unsuitable for
             enrollment or could interfere with participation in or completion of the study, per
             Investigator judgment.