A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis (ATLAS-PPX)

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 <1% or FIX level ≤2%)
• A minimum of 2 bleeding episodes requiring BPA treatment within the last 6 months prior to Screening for patients with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode requiring factor treatment within the last 12 months prior to Screening for patients without inhibitory antibodies to factor VIII or factor IX (Cohort B).
• Must meet either the definition of inhibitor or non-inhibitor patient as below:
• Inhibitor:Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to Screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria:
• Inhibitor titer of ≥0.6 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 patients in Cohort A patients must 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 meet each of the following criterion:
• Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at Screening and
• No use of bypassing agents 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 bypassing agents 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
• Willing and able to comply 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/μL
• 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 SC injection(s)
• Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment