A Study to Test a Medicine (Fitusiran) for Preventing Bleeds in People With Severe Hemophilia Who Previously Received Preventive Treatment With Emicizumab

Sanofi

Status and phase: Enrolling; Phase 4

Conditions: Hemophilia A

Treatments: Biological: Antithrombin concentrate (ATIIIC); Biological: Emicizumab; Drug: Fitusiran (SAR439774); Biological: Clotting factor concentrates (CFC) or bypassing agents (BPA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06145373

U1111-1280-7227 (Registry Identifier)

SFY17741

2022-502414-84 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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
  • Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of anamnestic response.

• Participants who are currently on the full labeled dose of emicizumab prophylaxis, irrespective of inhibitor/non-inhibitor status.

• Signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• 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
• Current or prior participation in a fitusiran trial
• Current or prior participation in a gene therapy trial
• AT activity <60% at Screening, as determined by central laboratory measurement
• Coexisting thrombophilic disorder - Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
• Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
• Presence of acute or chronic hepatitis B infection
• Known to be HIV positive with CD4 count <200 cells/μL.
• Reduced renal function

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

fitusiran

Experimental group

Description:

The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1. Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18. Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement. AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement.

Treatment:

Biological: Clotting factor concentrates (CFC) or bypassing agents (BPA)

Drug: Fitusiran (SAR439774)

Biological: Emicizumab

Biological: Antithrombin concentrate (ATIIIC)