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

NCT ID: NCT03417102

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-14
• Study Completion Date: 2021-06-23

Brief Summary

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).

Detailed 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.

Conditions

Hemophilia A; Hemophilia B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bypassing Agents (BPA) On-demand

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.

Group Type: ACTIVE_COMPARATOR

Bypassing agents

Intervention Type: DRUG

solution for injection; by intravenous (IV) injection

Fitusiran 80 mg Prophylaxis

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.

Group Type: EXPERIMENTAL

fitusiran

Intervention Type: DRUG

solution for injection; by subcutaneous (SC) injection

Interventions

fitusiran

solution for injection; by subcutaneous (SC) injection

Intervention Type: DRUG

Bypassing agents

solution for injection; by intravenous (IV) injection

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations, MD

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 0117

Phoenix, Arizona, United States

Investigational Site Number 0139

Los Angeles, California, United States

Investigational Site Number 0135

Orange, California, United States

Investigational Site Number 0137

San Diego, California, United States

Investigational Site Number 0128

Gainesville, Florida, United States

Investigational Site Number 0115

Jacksonville, Florida, United States

Investigational Site Number 0105

Miami, Florida, United States

Investigational Site Number 0103

Tampa, Florida, United States

Investigational Site Number 0119

New Orleans, Louisiana, United States

Investigational Site Number 0136

Baltimore, Maryland, United States

Investigational Site Number 0111

Las Vegas, Nevada, United States

Investigational Site Number 0104

Philadelphia, Pennsylvania, United States

Investigational Site Number 6101

Camperdown, , Australia

Investigational Site Number 6104

Clayton, , Australia

Investigational Site Number 1102

Montreal, , Canada

Investigational Site Number 8604

Beijing, , China

Investigational Site Number 8602

Guangzhou, , China

Investigational Site Number 8605

Hangzhou, , China

Investigational Site Number 8603

Shanghai, , China

Investigational Site Number 8601

Tianjin, , China

Investigational Site Number 3303

Lyon, , France

Investigational Site Number 3301

Rouen, , France

Investigational Site Number 4905

Frankfurt am Main, , Germany

Investigational Site Number 4906

Leipzig, , Germany

Investigational Site Number 9102

Bangalore, , India

Investigational Site Number 9108

India, , India

Investigational Site Number 9104

Jaipur, , India

Investigational Site Number 9106

Lucknow, , India

Investigational Site Number 9103

Pune, , India

Investigational Site Number 9111

Pune, , India

Investigational Site Number 9105

Vellore, , India

Investigational Site Number 3901

Florence, , Italy

Investigational Site Number 3904

Padua, , Italy

Investigational Site Number 8110

Japan, , Japan

Investigational Site Number 8103

Kita Kyushu-Shi, , Japan

Investigational Site Number 6003

Kota Kinabalu, , Malaysia

Investigational Site Number 6004

Malaysia, , Malaysia

Investigational Site Number 2701

Parktown, , South Africa

Investigational Site Number 2703

Polokwane, , South Africa

Investigational Site Number 2702

Port Elizabeth, , South Africa

Investigational Site Number 8202

Daejeon, , South Korea

Investigational Site Number 8203

Seoul, , South Korea

Investigational Site Number 8204

Seoul, , South Korea

Investigational Site Number 3402

Madrid, , Spain

Investigational Site Number 8803

Changhua, , Taiwan

Investigational Site Number 8804

Dawan, , Taiwan

Investigational Site Number 8805

Dawan, , Taiwan

Investigational Site Number 8801

Taipei, , Taiwan

Investigational Site Number 9002

Adana, , Turkey (Türkiye)

Investigational Site Number 9004

Akdeniz, , Turkey (Türkiye)

Investigational Site Number 9001

Ankara, , Turkey (Türkiye)

Investigational Site Number 9005

Istanbul, , Turkey (Türkiye)

Investigational Site Number 9003

Izmir, , Turkey (Türkiye)

Investigational Site Number 9006

Turkey, , Turkey (Türkiye)

Investigational Site Number 8003

Kyiv, , Ukraine

Investigational Site Number 8001

Kyiv, , Ukraine

Investigational Site Number 8002

Lviv, , Ukraine

Investigational Site Number 4407

London, , United Kingdom

Countries

United States; Australia; Canada; China; France; Germany; India; Italy; Japan; Malaysia; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Young G, Srivastava A, Kavakli K, Ross C, Sathar J, You CW, Tran H, Sun J, Wu R, Poloskey S, Qiu Z, Kichou S, Andersson S, Mei B, Rangarajan S. Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial. Lancet. 2023 Apr 29;401(10386):1427-1437. doi: 10.1016/S0140-6736(23)00284-2. Epub 2023 Mar 29.

Reference Type: DERIVED

PMID: 37003287 (View on PubMed)

The Lancet Haematology. The role of conferences in tackling inequalities. Lancet Haematol. 2022 Feb;9(2):e81. doi: 10.1016/S2352-3026(22)00008-4. No abstract available.

Reference Type: DERIVED

PMID: 35114155 (View on PubMed)

Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.

Reference Type: DERIVED

PMID: 34922648 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001463-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALN-AT3SC-003

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14768

Identifier Type: -

Identifier Source: org_study_id