A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis (ATLAS-PPX)
Phase 3
Completed
- Conditions
- Hemophilia
- Registration Number
- jRCT2080224181
- Lead Sponsor
- Sanofi K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- Male
- Target Recruitment
- 80
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/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 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
- Allocation: Not applicable (single arm) Masking: Open Label Design: Single arm
- Primary Outcome Measures
Name Time Method Annualized bleeding rate (ABR) Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period
- Secondary Outcome Measures
Name Time Method Annualized spontaneous bleeding rate Annualized spontaneous bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Annualized joint bleeding rate Annualized joint bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score fitusiran treatment period Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score on a scale of 0-100 with higher scores representing greater impairment
Change in Haem-A-QOL physical health score and total score in the fitusiran treatment periodABR in the onset period fitusiran onset period ABR in the fitusiran onset period
ABR in the treatment period fitusiran treatment period ABR in the fitusiran treatment period
Annualized weight-adjusted consumption of factor/BPA Annualized weight-adjusted consumption of factor/BPA
Number of patients reported with treatment emergent adverse events Number of patients reported with treatment emergent adverse events
Trial Locations
- Locations (1)
Australia/China/Denmark/France/Ireland/Israel/Italy/Republic of Korea/Malaysia/Mexico/Turkey/Ukraine/United Kingdom/United States/Japan
Location not specified
Australia/China/Denmark/France/Ireland/Israel/Italy/Republic of Korea/Malaysia/Mexico/Turkey/Ukraine/United Kingdom/United States/Japan