Brief Title
A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
Official Title
ATLAS-A/B: A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients With Hemophilia A or B, Without Inhibitory Antibodies to Factor VIII or IX
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).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
Secondary Outcome
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period
Condition
Hemophilia A
Intervention
fitusiran
Study Arms / Comparison Groups
Factor On-demand
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
120
Start Date
March 1, 2018
Completion Date
July 14, 2021
Primary Completion Date
January 26, 2021
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.
Gender
Male
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Sciences & Operations, MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03417245
Organization ID
EFC14769
Secondary IDs
ALN-AT3SC-004
Responsible Party
Sponsor
Study Sponsor
Genzyme, a Sanofi Company
Study Sponsor
Clinical Sciences & Operations, MD, Study Director, Sanofi
Verification Date
March 2022