Phase 3 N=57 Randomized Treatment

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

Hemophilia A · Hemophilia B

Bottom Line

View on ClinicalTrials.gov: NCT03417102 ↗

Enrolled (actual)

Serious AEs

20.0%

Results posted

Dec 2021

Primary outcome: Primary: Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period — 18.071; 1.666 episodes per participant per year — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: fitusiran (Drug); Bypassing agents (Drug)
Age: Pediatric, Adult, Older Adult · 12+ yrs
Sex: Male
Sponsor: Genzyme, a Sanofi Company
Primary completion: Nov 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period	18.071; 1.666	<0.0001 sig
PRIMARY Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period	18.1; 1.7	—
SECONDARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period	18.819; 2.024	<0.0001 sig
SECONDARY Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period	18.8; 2.0	—
SECONDARY Estimated Annualized Spontaneous Bleeding Rate for Treated Bleeds During Efficacy Period	15.675; 0.872	<0.0001 sig
SECONDARY Observed Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period	15.6; 0.9	—
SECONDARY Estimated Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period	13.759; 1.349	<0.0001 sig
SECONDARY Observed Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period	13.8; 1.4	—
SECONDARY Health-related Quality of Life (HRQOL): Change From Baseline in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Month 9	-1.94; -30.67	<0.0001 sig
SECONDARY Health-related Quality of Life (HRQOL): Change From Baseline in Haem-A-QOL Total Score at Month 9	-0.42; -15.27	<0.0001 sig
SECONDARY Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Onset Period	25.149; 4.426	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	11; 38; 5; 7	—

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).

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 ( =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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03417102). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.