A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis

• Status: Active, not recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: Male

Summary

Primary Objective:

To characterize the frequency of bleeding episodes while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor 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 patients ≥17 years of age

• To characterize the frequency of bleeding episodes during the onset and treatment periods in patients receiving fitusiran

• To characterize the safety and tolerability of fitusiran

• Annualized weight-adjusted consumption of factor/BPA

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genzyme, a Sanofi Company
• Treatments: Factor VIII

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 <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