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

Hemophilia Clinical Trial

— ATLAS-NEO  

Official title:

A Phase 3, Single-arm, Multicenter, Multinational, Open-label, One-way Crossover Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged ≥ 12 Years With Severe Hemophilia A or B With or Without Inhibitory Antibodies to Factor VIII or IX

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05662319
• Other study ID #: EFC17574
• Secondary ID: U1111-1275-95842
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2023
• Est. completion date: March 1, 2028

Study information

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

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: March 1, 2028
• Est. primary completion date: April 15, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Drug:
• Fitusiran
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous (SC)
• Clotting factor concentrates (CFC) or bypassing agents (BPA)
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)
• Antithrombin concentrate (ATIIIC)
Antithrombin III (ATC code: B01AB02) Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)

Locations

Country	Name	City	State
Canada	Investigational Site Number : 1240001	Hamilton	Ontario
Canada	Investigational Site Number : 1240002	Hamilton	Ontario
China	Investigational Site Number : 1560003	Beijing
China	Investigational Site Number : 1560001	Guangzhou
China	Investigational Site Number : 1560002	Jinan
France	Investigational Site Number : 2500003	Kremlin Bicetre
France	Investigational Site Number : 2500002	Lille
France	Investigational Site Number : 2500001	Paris
Germany	Investigational Site Number : 2760001	Berlin
Germany	Investigational Site Number : 2760002	Hamburg
Greece	Investigational Site Number : 3000001	Athens
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number : 3000003	Thessaloniki
India	Investigational Site Number : 3560004	Bangalore
India	Investigational Site Number : 3560007	Bhubaneswar
India	Investigational Site Number : 3560001	Pune-411011
India	Investigational Site Number : 3560006	Punjab
India	Investigational Site Number : 3560003	Vellore
Italy	Investigational Site Number : 3800001	Milano
Italy	Investigational Site Number : 3800002	Roma
Italy	Investigational Site Number : 3800003	Rozzano	Lombardia
Japan	Investigational Site Number : 3920001	Kashihara-shi	Nara
Japan	Investigational Site Number : 3920003	Nagoya
Japan	Investigational Site Number : 3920002	Saitama-shi
Japan	Investigational Site Number : 3920004	Shinjuku-ku	Tokyo
Korea, Republic of	Investigational Site Number : 4100003	Incheon	Incheon-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Mexico	Investigational Site Number : 4840004	Chihuahua
Mexico	Investigational Site Number : 4840002	Monterrey	Nuevo León
Mexico	Investigational Site Number : 4840001	Veracruz
Poland	Investigational Site Number : 6160002	Krakow	Malopolskie
Poland	Investigational Site Number : 6160004	Lodz	Lódzkie
Poland	Investigational Site Number : 6160001	Warszawa	Mazowieckie
Saudi Arabia	Investigational Site Number : 6820002	Jeddah
South Africa	Investigational Site Number : 7100003	Benoni
South Africa	Investigational Site Number : 7100001	Parktown
Spain	Investigational Site Number : 7240002	La Coruña	A Coruña [La Coruña]
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240003	Zaragoza
Taiwan	Investigational Site Number : 1580002	Taichung
Taiwan	Investigational Site Number : 1580001	Taipei
Taiwan	Investigational Site Number : 1580003	Taipei
Turkey	Investigational Site Number : 7920002	Adana
Turkey	Investigational Site Number : 7920004	Akdeniz
Turkey	Investigational Site Number : 7920001	Capa
Turkey	Investigational Site Number : 7920003	Izmir
United States	University Hospitals of Cleveland Site Number : 8400001	Cleveland	Ohio
United States	Children's Medical Center of Dallas Site Number : 8400018	Dallas	Texas
United States	Hackensack University Site Number : 8400009	Hackensack	New Jersey
United States	The Gulf States Hemophilia and Thrombophilia Center Site Number : 8400002	Houston	Texas
United States	Medical College of Wisconsin Site Number : 8400007	Milwaukee	Wisconsin
United States	University of Minnesota Site Number : 8400016	Minneapolis	Minnesota
United States	Northwell Health Hemostasis and Thrombosis Center Site Number : 8400015	New Hyde Park	New York
United States	Center for Inherited Blood Disorders (CIBD) Site Number : 8400012	Orange	California
United States	UPMC Children's Hospital of Pittsburgh-4401 Penn Ave Site Number : 8400017	Pittsburgh	Pennsylvania
United States	University Of Utah Health Sciences Center Site Number : 8400006	Salt Lake City	Utah
United States	University of California San Diego Site Number : 8400011	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Germany,  Greece,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Saudi Arabia,  South Africa,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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 (primary efficacy period) and Day -168 to Day -1 (SOC period)
Secondary	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	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 (primary efficacy period) and Day -168 to Day -1 (SOC period)
Secondary	Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC 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.; A spontaneous bleeding episode is a bleeding event that occurs for no apparent or known reason, particularly into the joints, muscles, and soft tissues.	Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
Secondary	Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC 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.; A joint bleeding episode is characterized by an unusual sensation in the joint ("aura") in combination with 1) increasing swelling or warmth over the skin over the joint, 2) increasing pain, or 3) progressive loss of range of motion or difficulty in using the limb as compared with baseline.	Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
Secondary	Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis	The Haem-A-QoL will be provided to participants =17 years of age and includes 46 items contributing to 10 QoL domains (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership, and sexuality). Scoring for each item is based on a 5-point Likert scale (never, rarely, sometimes, often, and all the time), and higher scores represent greater impairment.	Day 1 (D1) to Day 505, and from D1 to Day 1009, and during SOC from Day-168 to D-1
Secondary	Annualized bleeding rate (ABR) in the fitusiran 18-month 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 1 to Day 505
Secondary	Annualized bleeding rate (ABR) in the fitusiran 36-month treatment 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 1 to Day 1009
Secondary	Annualized weight-adjusted consumption of CFC/BPA	All CFC or BPA doses (including doses per kg body weight) administered during the study treatment will be recorded	Day -168 until Day 1009
Secondary	Number of participants with adverse events	All AEs (serious or nonserious) will be collected from the signing of the informed consent form (ICF) until last AT follow up visit.	Date of signed ICF (Day -228 to Day -169) until last visit (approximately 50 months after date of signed ICF)