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

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06145373
• Other study ID #: SFY17741
• Secondary ID: 2022-502414-84U1
• Status: Recruiting
• Phase: Phase 1
• Start date: March 1, 2024
• Est. completion date: May 19, 2028

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 19, 2028
• Est. primary completion date: September 19, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

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
• Antithrombin concentrate (ATIIIC)
Pharmaceutical form:Solution for injection-Route of administration:Intravenous (IV) injection
• Emicizumab
Pharmaceutical form:Solution for injection-Route of administration:SC injection

Locations

Country	Name	City	State
Taiwan	Investigational Site Number : 1580001	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Emicizumab concentrations in plasma	Emicizumab concentrations in plasma will be reported	Up to Month 4 of fitusiran treatment
Secondary	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
Secondary	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]
Secondary	Participants' treatment preferences (via the Preference Questionnaire)	The Preference questionnaire Data will be reported	At Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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)