A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients With Inhibitors (ATLAS-INH)

Genzyme

Status and phase: Completed; Phase 3

Conditions: Hemophilia B; Hemophilia A

Treatments: Drug: fitusiran; Drug: Bypassing agents

Study type: Interventional

Funder types: Industry

Identifiers

NCT03417102

ALN-AT3SC-003 (Other Identifier)

2016-001463-36 (EudraCT Number)

EFC14768

Details and patient eligibility

About

The purpose of this study was to determine the frequency of bleeding episodes in participants receiving fitusiran as prophylactic treatment of hemophilia compared to participants who were assigned to continue with their regular medication. In addition, the study assessed safety, quality of life, pharmacodynamics (PD), and pharmacokinetics (PK).

Full description

The duration of treatment with fitusiran was 9 months. The estimated total time on study, inclusive of screening, for each participant was up to 11 months for all participants who enroll in the extension study and participants in the on-demand arm who did not enroll in the extension study. The estimated total time on study was up to 17 months in fitusiran treatment arm participants who did not enroll in the extension study due to the requirement for up to an additional 6 months of follow-up monitoring for antithrombin levels.

Enrollment: 60 patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males, greater than or equal to (>=) 12 years of age.

• Severe hemophilia A or B with inhibitors.

  • (Severity confirmed by a central laboratory where coagulation factor VIII (FVIII) level was less than (<)1% or factor IX (FIX) level was less than or equal to [<=]2% at Screening; Inhibitors defined as inhibitor titer of >=0.6 Bethesda units per milliliter [BU/mL] or as evidenced by medical records).

• A minimum of 6 bleeding episodes requiring BPA 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.

Exclusion criteria

• Known co-existing bleeding disorders other than hemophilia A or B.
• Antithrombin (AT) activity <60% at Screening.
• Co-existing thrombophilic disorder.
• Clinically significant liver disease.
• Active hepatitis C virus infection.
• HIV positive with a cluster of differentiation-4 count of <200 cells/microliter.
• History of arterial or venous thromboembolism.
• Inadequate renal function.
• History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine.
• History of intolerance to SC injection(s).
• Any other conditions or comorbidities that would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgement.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

60 participants in 2 patient groups

Bypassing Agents (BPA) On-demand

Active Comparator group

Description:

Participants received On-demand BPAs (use of these agents, as needed, for episodic bleeding episodes, and not on a regular regimen intended to prevent spontaneous bleeding) per Investigator discretion from Day 1 for treatment of breakthrough bleeding episodes, up to a total of 9 months.

Treatment:

Drug: Bypassing agents

Fitusiran 80 mg Prophylaxis

Experimental group

Description:

Participants received Fitusiran 80 mg subcutaneously (SC) as prophylaxis once monthly from Day 1, along with the on-demand BPAs (per investigator's discretion and within bleeding dosing guidelines) for treatment of breakthrough bleeding episodes, up to a total of 9 months.

Treatment:

Drug: fitusiran