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

An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥18 Years of Age With Severe Hemophilia A, With or Without Inhibitors

This is an exploratory, single group, Phase 1, 1-arm 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 ≥18 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 a transition 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 up to 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.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: Fitusiran (SAR439774); Biological: Clotting factor concentrates (CFC) or bypassing agents (BPA); Biological: Antithrombin concentrate (ATIIIC); Biological: Emicizumab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 10041
    • Recruiting
    • Investigational Site Number : 1580001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male participants must be ≥18 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.
• Capable of giving signed informed consent 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: fitusiran; 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.

Drug: Fitusiran (SAR439774); Pharmaceutical form:Solution for injection-Route of administration:Subcutaneous (SC) injection; Other Names: SAR439774; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From Day 1 up to Month 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The peak thrombin generation (TG) - pre fitusiran treatment	Central laboratory assessments (peak TG) will be reported for pre-fitusiran period	From Month -2 up to Day 1
The peak TG during fitusiran treatment	Central laboratory assessments (peak TG) will be reported for fitusiran treatment period	From Day 1 up to Month 4
The peak antithrombin (AT) levels during pre-fitusiran treatment	Central laboratory assessments (peak AT) will be reported for pre-fitusiran treatment period	From Month -2 up to Day 1
The peak AT levels during fitusiran prophylaxis	Central laboratory assessments (peak AT) will be reported for fitusiran treatment	From Day 1 up to Month 4
Emicizumab concentrations in plasma	Emicizumab concentrations in plasma will be reported	Up to Month 4 of fitusiran treatment
Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment	Incidence, severity, and seriousness of AEs will be reported	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	The three domains of effectiveness, convenience, and global satisfaction will be reported	From approximately Month -2 to Month 19 [end of study (EoS) visit]
Participants' treatment preferences (via the Preference Questionnaire)	The Preference questionnaire Data will be reported	At Month 12
Change in participants' pain intensity during the fitusiran treatment period (via the PROMIS v2.0 Pain Intensity 3a questionnaire) over time	The data for participants' pain intensity via PROMIS v2.0 Pain Intensity 3a questionnaire will be reported	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	Participants' physical functioning and physical activity data during the fitusiran treatment period will be collected via the International Physical Activity Questionnaire and reported	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	HJHS during the fitusiran treatment period will be reported	From approximately Month - 2 to Month 19 (EoS) visit
Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis	The frequency of treated bleeding episodes will be reported	From Month 4 up to Month 18 (14-month extension period)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): September 19, 2026
• Study Completion (Estimated): May 19, 2028

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: SFY17741; 2022-502414-84 (Registry Identifier: CTIS); U1111-1280-7227 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No