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

Official title

An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥12 Years of Age With Severe Hemophilia A, With or Without Inhibitors

Overview

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.

Interventions

• Drug Fitusiran (SAR439774)
  Pharmaceutical form:Solution for injection-Route of administration:Subcutaneous (SC) injection
• Biological Clotting factor concentrates (CFC) or bypassing agents (BPA)
  Pharmaceutical form: Solution for injection-Route of administration: Intravenous (IV) injection
• Biological Antithrombin concentrate (ATIIIC)
  Pharmaceutical form:Solution for injection-Route of administration:Intravenous (IV) injection
• Biological Emicizumab
  Pharmaceutical form:Solution for injection-Route of administration:SC injection

Primary outcome measures

• Number of participants with Adverse events (AEs) during the fitusiran treatment [Time frame: From Day 1 up to Month 4]

Secondary outcome measures (12)

• The peak thrombin generation (TG) - pre fitusiran treatment [Time frame: From Month -2 up to Day 1]
• The peak TG during fitusiran treatment [Time frame: From Day 1 up to Month 4]
• The antithrombin (AT) levels during pre-fitusiran treatment [Time frame: From Month -2 up to Day 1]
• The AT levels during fitusiran prophylaxis [Time frame: From Day 1 up to Month 4]
• Emicizumab concentrations in plasma [Time frame: Up to Month 4 of fitusiran treatment]
• Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment [Time frame: From Day 1 up to Month 18]
• Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores [Time frame: From approximately Month -2 to Month 19 [end of study (EoS) visit]]
• Participants' treatment preferences (via the Preference Questionnaire) [Time frame: At Month 12]
• Change in adult participants' pain intensity during the fitusiran treatment period over time [Time frame: From approximately Month - 2 to Month 19 (EoS) visit]
• Change in adolescent participants' pain intensity during the fitusiran treatment period over time [Time frame: From approximately Month - 2 to Month 19 (EoS) visit]
• Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time [Time frame: From approximately Month - 2 to Month 19 (EoS) visit]
• Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time [Time frame: From approximately Month - 2 to Month 19 (EoS) visit]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Children's Hospital Los Angeles- Site Number : 8400005 — Los Angeles

Taiwan · 1 center

• Investigational Site Number : 1580001 — Taipei

Identifiers

NCT: NCT06145373 · SFY17741 · 2022-502414-84 · U1111-1280-7227

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗