A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia

NCT05662319 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EFC17574U1111-1275-95842022-500221-33
• Study Type: interventional
• Target: 91
• Locations: 17 countries
• Sites: 50

Brief Summary

This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia. The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment. The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include:

• A screening period up to approximately 60 days,
• A standard of care (SOC) period of approximately 6 study months (24 weeks),
• A fitusiran treatment period of approximately 36 study months (144 weeks),
• An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery. The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study

Conditions

Hemophilia

Outcome Measures

Primary Outcomes (1)

• Annualized bleeding rate (ABR) in the fitusiran primary efficacy period

  A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.

  Day 169 to Day 505 (since the first dose of fitusiran)

Secondary Outcomes (9)

• Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on prophylaxis standard of care (SOC) in the SOC period

  Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)

• Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on on-demand standard of care (SOC) in the SOC period

  Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)

• Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC period

  Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)

• Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC period

  Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)

• Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis

  Day 1 (D1) to Day 505, and from D1 to Day 1009, and during SOC from Day-168 to D-1

Study Arms (1)

All participants

EXPERIMENTAL

In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine. .

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

Interventions

Fitusiran DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous (SC)

All participants

Clotting factor concentrates (CFC) or bypassing agents (BPA) DRUG

* Coagulation factor VIII (ATC code: B02BD02) * Coagulation factor IX (ATC code: B02BD04) * Coagulation factor VIIa (ATC code: B02BD08) * Factor VIII inhibitor bypassing activity (ATC code: B02BD03) Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)

All participants

Antithrombin concentrate (ATIIIC) DRUG

Antithrombin III (ATC code: B01AB02) Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)

All participants

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of severe congenital hemophilia A or B (FVIII \<1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
• For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
• Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements

You may not qualify if:

• Known co-existing bleeding disorders other than congenital hemophilia A or B
• History of arterial or venous thromboembolism, not associated with an indwelling venous access
• History of intolerance to SC injection(s).
• Current participation in immune tolerance induction therapy (ITI)
• Prior gene therapy
• Current or prior participation in a fitusiran trial
• Current or prior participation in a gene therapy trial
• Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
• Presence of clinically significant liver disease AT activity \<60% at Screening
• Co-existing 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (50)

Center for Inherited Blood Disorders (CIBD) Site Number : 8400012

Orange, California, 92868-4306, United States

Location

M Health Fairview University of Minnesota Medical Center - West Bank- Site Number : 8400016

Minneapolis, Minnesota, 55454, United States

Location

Hackensack University Site Number : 8400009

Hackensack, New Jersey, 07601, United States

Location

Northwell Health Hemostasis and Thrombosis Center Site Number : 8400015

New Hyde Park, New York, 11040, United States

Location

University Hospitals of Cleveland Site Number : 8400001

Cleveland, Ohio, 44106, United States

Location

UPMC Children's Hospital of Pittsburgh-4401 Penn Ave Site Number : 8400017

Pittsburgh, Pennsylvania, 15224-1334, United States

Location

Children's Medical Center Dallas- Site Number : 8400018

Dallas, Texas, 75235, United States

Location

Gulf States Hemophilia and Thrombophilia Center- Site Number : 8400002

Houston, Texas, 77030, United States

Location

Investigational Site Number : 1240001

Hamilton, Ontario, L8N 3Z5, Canada

Location

Investigational Site Number : 1240002

Hamilton, Ontario, L8N 3Z5, Canada

Location

Investigational Site Number : 1240004

Toronto, Ontario, M5G 1X8, Canada

Location

Investigational Site Number : 1560003

Beijing, 100045, China

Location

Investigational Site Number : 1560001

Guangzhou, 510515, China

Location

Investigational Site Number : 1560002

Jinan, 250013, China

Location

Investigational Site Number : 2500003

Le Kremlin-Bicêtre, 94275, France

Location

Investigational Site Number : 2500002

Lille, 59037, France

Location

Investigational Site Number : 2500001

Paris, 75015, France

Location

Investigational Site Number : 2760001

Berlin, 10249, Germany

Location

Investigational Site Number : 2760002

Hamburg, 20246, Germany

Location

Investigational Site Number : 3000001

Athens, 115 27, Greece

Location

Investigational Site Number : 3000002

Athens, 11527, Greece

Location

Investigational Site Number : 3560004

Bangalore, 560 034, India

Location

Investigational Site Number : 3560007

Bhubaneswar, 751019, India

Location

Investigational Site Number : 3560001

Pune-411011, 411 011, India

Location

Investigational Site Number : 3560006

Punjab, 141008, India

Location

Investigational Site Number : 3560003

Vellore, 632004, India

Location

Investigational Site Number : 3800003

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number : 3800001

Milan, 20122, Italy

Location

Investigational Site Number : 3920003

Nagoya, Aichi-ken, 4668560, Japan

Location

Investigational Site Number : 3920001

Kashihara-shi, Nara, 634-8522, Japan

Location

Investigational Site Number : 3920002

Saitama-shi, Saitama, 330-8777, Japan

Location

Investigational Site Number : 4840002

Monterrey, Nuevo León, 64460, Mexico

Location

Investigational Site Number : 4840004

Chihuahua City, 31000, Mexico

Location

Investigational Site Number : 4840001

Veracruz, 91900, Mexico

Location

Investigational Site Number : 6160002

Krakow, Lesser Poland Voivodeship, 30-688, Poland

Location

Investigational Site Number : 6160004

Lodz, Lódzkie, 93-510, Poland

Location

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, 02-776, Poland

Location

Investigational Site Number : 6820002

Jeddah, 21423, Saudi Arabia

Location

Investigational Site Number : 7100003

Johannesburg, 1501, South Africa

Location

Investigational Site Number : 7100001

Parktown, 2193, South Africa

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 05278, South Korea

Location

Investigational Site Number : 7240002

A Coruña, A Coruña [La Coruña], 15006, Spain

Location

Investigational Site Number : 7240003

Zaragoza, 50009, Spain

Location

Investigational Site Number : 1580001

Taipei, 100, Taiwan

Location

Investigational Site Number : 1580003

Taipei, 11031, Taiwan

Location

Investigational Site Number : 7920002

Adana, 01130, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Akdeniz, 07059, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Çapa, 34390, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Izmir, TR-35100, Turkey (Türkiye)

Location

Related Links

• EFC17574 Plain Language Results Summaries

MeSH Terms

Conditions

Hemophilia A

Interventions

fitusiran

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: One way cross-over

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: December 22, 2022
• Study Start: February 1, 2023
• Primary Completion (Estimated): March 25, 2027
• Study Completion (Estimated): January 25, 2029
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); GR (2); TW (2); TU (4); CN (3); SA (1); CA (3); PL (3); ZA (2); JP (3); KR (2); FR (3); IN (5); US (8); IT (2); ES (2); ME (3)