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

Sanofi

Status and phase: Active, not recruiting; Phase 3

Conditions: Hemophilia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05662319

EFC17574

U1111-1275-9584 (Registry Identifier)

2022-500221-33 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 79 patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Crossover Assignment

Masking: None (Open label)

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79 participants in 1 patient group

All participants

Experimental group

Description:

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. .

Treatment:

Drug: Clotting factor concentrates (CFC) or bypassing agents (BPA)

Drug: Antithrombin concentrate (ATIIIC)

Drug: Fitusiran