A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
- Conditions
- Hemophilia
- Registration Number
- JPRN-jRCT2080224181
- Lead Sponsor
- Sanofi K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- Male
- Target Recruitment
- 80
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
- 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/uL
- 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>Annualized bleeding rate (ABR)<br>Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period<br>[Time Frame: 13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period)]
- Secondary Outcome Measures
Name Time Method