A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors

NCT ID: NCT03417245

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2021-07-14

Brief Summary

Primary Objective:

-To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by the frequency of bleeding episodes.

Secondary Objectives:

• To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by:

• The frequency of spontaneous bleeding episodes.
• The frequency of joint bleeding episodes.
• Health-related quality of life (HRQOL) in participants >=17 years of age.
• To determine the frequency of bleeding episodes during the onset period.
• To determine the safety and tolerability of fitusiran.

Detailed Description

The duration of treatment with fitusiran was 9 months. The estimated total time on study, inclusive of screening, was up to 11 months for all participants in the factor on-demand arm and for participants in the fitusiran arm who enrolled in the extension study (LTE15174). The estimated total time on the study was up to 17 months for participants in the fitusiran treatment arm 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.

Participants who completed the study will be eligible for an open-label extension study LTE15174 (NCT03754790).

Conditions

Hemophilia A; Hemophilia B

Study Design

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

Study Groups

Factor On-demand

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

Group Type: EXPERIMENTAL

factor concentrates

Intervention Type: DRUG

by intravenous (IV) injection

Fitusiran 80 mg Prophylaxis

Participants received open-label fitusiran 80 milligram (mg) administered subcutaneously (SC) as prophylaxis once monthly from Day 1 up to a total of 9 months. Participants received on-demand factor concentrates (per investigator's discretion and within bleeding dosing guidelines) for the treatment of breakthrough bleeding episodes.

Group Type: EXPERIMENTAL

fitusiran

Intervention Type: DRUG

by SC injection

factor concentrates

Intervention Type: DRUG

by intravenous (IV) injection

Interventions

fitusiran

by SC injection

Intervention Type: DRUG

factor concentrates

by intravenous (IV) injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males, >=12 years of age.
• Severe hemophilia A or B without inhibitors.

• Severity confirmed by a central laboratory where FVIII level was less than (<) 1 percent (%) or Factor IX (FIX) level was less than or equal to (<=) 2% at Screening.
• On-demand use of factor concentrate to manage bleeding episodes for at least the last 6 months prior to Screening, and meet each of the following criterion:

• Nijmegen modified Bethesda assay inhibitor titer of <0.6 Bethesda units per milliliter (BU/mL) at Screening.
• No use of Bypassing agents to treat bleeding episodes for at least the last 6 months prior to Screening.
• No history of immune tolerance induction therapy within the last 3 years prior to Screening.
• A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to Screening.
• Willing and complied 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, i.e., Von Willebrand's disease, additional factor deficiencies, or platelet disorders.
• 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 (GalNAc).
• 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 judgment.

• 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 0140

Little Rock, Arkansas, United States

Investigational Site Number 128

Gainesville, Florida, United States

Investigational Site Number 103

Tampa, Florida, United States

Investigational Site Number 102

Chicago, Illinois, United States

Investigational Site Number 119

New Orleans, Louisiana, United States

Investigational Site Number 125

Ann Arbor, Michigan, United States

Investigational Site Number 111

Las Vegas, Nevada, United States

Investigational Site Number 110

Akron, Ohio, United States

Investigational Site Number 6101

Camperdown, , Australia

Investigational Site Number 6103

Murdoch, , Australia

Investigational Site Number 6104

Prahran, , Australia

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 4501

Copenhagen, , Denmark

Investigational Site Number 3303

Lyon, , France

Investigational Site Number 3305

Paris, , France

Investigational Site Number 3301

Rouen, , France

Investigational Site Number 4904

Berlin, , Germany

Investigational Site Number 4905

Frankfurt am Main, , Germany

Investigational Site Number 4906

Leipzig, , Germany

Investigational Site Number 3602

Budapest, , Hungary

Investigational Site Number 9102

Bangalore, , India

Investigational Site Number 9104

Jaipur, , India

Investigational Site Number 9106

Lucknow, , India

Investigational Site Number 9109

Mumbai, , India

Investigational Site Number 9108

Mumbai, , India

Investigational Site Number 9111

Mumbai, , India

Investigational Site Number 9103

Pune, , India

Investigational Site Number 9105

Vellore, , India

Investigational Site Number 9701

Ramat Gan, , Israel

Investigational Site Number 3904

Padua, , Italy

Investigational Site Number 8105

Isehara, , Japan

Investigational Site Number 8104

Saitama, , Japan

Investigational Site Number 6004

Ampang, , Malaysia

Investigational Site Number 6002

Johor Bahru, , Malaysia

Investigational Site Number 6003

Kota Kinabalu, , Malaysia

Investigational Site Number 2701

Parktown, , South Africa

Investigational Site Number 2702

Port Elizabeth, , South Africa

Investigational Site Number 8201

Busan, , South Korea

Investigational Site Number 8202

Daejeon, , South Korea

Investigational Site Number 8204

Seoul, , South Korea

Investigational Site Number 3402

Madrid, , Spain

Investigational Site Number 8807

Taichung, , Taiwan

Investigational Site Number 8805

Taichung, , Taiwan

Investigational Site Number 8804

Taipei, , Taiwan

Investigational Site Number 8801

Taipei, , Taiwan

Investigational Site Number 8808

Taoyuan District, , Taiwan

Investigational Site Number 9002

Adana, , Turkey (Türkiye)

Investigational Site Number 9004

Antalya, , Turkey (Türkiye)

Investigational Site Number 9008

Gaziantep, , Turkey (Türkiye)

Investigational Site Number 9005

Istanbul, , Turkey (Türkiye)

Investigational Site Number 9003

Izmir, , Turkey (Türkiye)

Investigational Site Number 9009

Kayseri, , Turkey (Türkiye)

Investigational Site Number 9006

Samsun, , Turkey (Türkiye)

Investigational Site Number 8001

Kyiv, , Ukraine

Investigational Site Number 8003

Kyiv, , Ukraine

Investigational Site Number 8002

Lviv, , Ukraine

Investigational Site Number 8005

Mykolaiv, , Ukraine

Investigational Site Number 4402

Glasgow, , United Kingdom

Investigational Site Number 4407

London, , United Kingdom

Investigational Site Number 4401

London, , United Kingdom

Countries

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

References

Srivastava A, Rangarajan S, Kavakli K, Klamroth R, Kenet G, Khoo L, You CW, Xu W, Malan N, Frenzel L, Bagot CN, Stasyshyn O, Chang CY, Poloskey S, Qiu Z, Andersson S, Mei B, Pipe SW. Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. 2023 May;10(5):e322-e332. doi: 10.1016/S2352-3026(23)00037-6. Epub 2023 Mar 29.

Reference Type: DERIVED

PMID: 37003278 (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

ALN-AT3SC-004

Identifier Type: OTHER

Identifier Source: secondary_id

2016-001464-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC14769

Identifier Type: -

Identifier Source: org_study_id