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

• Sponsor: Sanofi (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06145373
• Collaborator: (none)
• Enrollment: 20
• Arm: 1
• Anticipated Duration (Months): 49.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A	Drug: Fitusiran (SAR439774); Biological: Clotting factor concentrates (CFC) or bypassing agents (BPA); Biological: Antithrombin concentrate (ATIIIC); Biological: Emicizumab	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 ≥18 Years of Age With Severe Hemophilia A, With or Without Inhibitors
• Anticipated Study Start Date: Dec 15, 2023
• Anticipated Primary Completion Date: May 15, 2026
• Anticipated Study Completion Date: Jan 18, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

   Incidence, severity, and seriousness, of AEs occurred during fitusiran treatment period will be reported

Secondary Outcome Measures

1. The peak thrombin generation (TG) - pre fitusiran treatment [From Month -2 up to Day 1]

   Central laboratory assessments (peak TG) will be reported for pre-fitusiran period

2. The peak TG during fitusiran treatment [From Day 1 up to Month 4]

   Central laboratory assessments (peak TG) will be reported for fitusiran treatment period

3. The peak antithrombin (AT) levels during pre-fitusiran treatment [From Month -2 up to Day 1]

   Central laboratory assessments (peak AT) will be reported for pre-fitusiran treatment period

4. The peak AT levels during fitusiran prophylaxis [From Day 1 up to Month 4]

   Central laboratory assessments (peak AT) will be reported for fitusiran treatment

5. Emicizumab concentrations in plasma [Up to Month 4 of fitusiran treatment]

   Emicizumab concentrations in plasma will be reported

6. Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment [From Day 1 up to Month 18]

   Incidence, severity, and seriousness of AEs will be reported

7. Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores [From approximately Month -2 to Month 19 [end of study (EoS) visit]]

   The three domains of effectiveness, convenience, and global satisfaction will be reported

8. Participants' treatment preferences (via the Preference Questionnaire) [At Month 12]

   The Preference questionnaire Data will be reported

9. Change in participants' pain intensity during the fitusiran treatment period (via the PROMIS v2.0 Pain Intensity 3a questionnaire) over time [From approximately Month - 2 to Month 19 (EoS) visit]

   The data for participants' pain intensity via PROMIS v2.0 Pain Intensity 3a questionnaire will be reported

10. Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time [From approximately Month - 2 to Month 19 (EoS) visit]

    Participants' physical functioning and physical activity data during the fitusiran treatment period will be collected via the International Physical Activity Questionnaire and reported

11. Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time [From approximately Month - 2 to Month 19 (EoS) visit]

    HJHS during the fitusiran treatment period will be reported

12. Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis [From Month 4 up to Month 18 (14-month extension period)]

    The frequency of treated bleeding episodes will be reported

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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 XE " ICF " \f

Abbreviation \t "informed consent form" ) 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT06145373
• Other Study ID Numbers: SFY17741; 2022-502414-84; U1111-1280-7227
• First Posted: Nov 24, 2023
• Last Update Posted: Nov 24, 2023
• Last Verified: Nov 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemophilia A; Antithrombins; Antithrombin III

Study Results

No Results Posted as of Nov 24, 2023