This is an exploratory, single group, Phase 4, study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.
This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥12 years, who were previously receiving emicizumab prophylaxis.
Study details include:
* The study duration will be up to approximately 28 months:
* There will be an approximately 2-month screening period. * There will be an approximately 2-month period before fitusiran treatment starts (pre-fitusiran treatment period) * The fitusiran treatment duration will be up to 18-months (fitusiran treatment period) * The antithrombin (AT) follow-up (FU) period will be approximately 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%). * The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.
Male participants must be ≥12 years of age inclusive, at the time of signing the informed consent
Diagnosis of severe congenital hemophilia A (FVIII < 1%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
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
Known coexisting bleeding disorders
History of antiphospholipid antibody syndrome.
History of arterial or venous thromboembolism, atrial fibrillation, significant valvular disease, myocardial infarction, angina, transient ischemic attack, or stroke. Participants who have experienced thrombosis associated with indwelling venous access may be enrolled.
Presence of clinically significant liver disease
Single group
Fitusiran (SAR439774)
DrugPharmaceutical form:Solution for injection-Route of administration:Subcutaneous (SC) injection
Clotting factor concentrates (CFC) or bypassing agents (BPA)
Biological/VaccinePharmaceutical form: Solution for injection-Route of administration: Intravenous (IV) injection
Antithrombin concentrate (ATIIIC)
Biological/VaccinePharmaceutical form:Solution for injection-Route of administration:Intravenous (IV) injection
Emicizumab
Biological/VaccinePharmaceutical form:Solution for injection-Route of administration:SC injection
Number of participants with Adverse events (AEs) during the fitusiran treatment
Incidence, severity, and seriousness, of AEs occurred during fitusiran treatment period will be reported
The peak thrombin generation (TG) - pre fitusiran treatment
Central laboratory assessments (peak TG) will be reported for pre-fitusiran period
The peak TG during fitusiran treatment
Central laboratory assessments (peak TG) will be reported for fitusiran treatment period
The antithrombin (AT) levels during pre-fitusiran treatment
Central laboratory assessments (AT) will be reported for pre-fitusiran treatment period
The AT levels during fitusiran prophylaxis
Central laboratory assessments (AT) will be reported for fitusiran treatment
