Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B

Hemophilia Clinical Trial

— ATLAS-PEDS  

Official title:

ATLAS-PEDS: An Open-label, Multinational Study of Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03974113
• Other study ID #: EFC15467
• Secondary ID: U1111-1223-43682
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 28, 2020
• Est. completion date: August 1, 2028

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• To confirm appropriate dose levels of fitusiran when administered to male pediatric participants (ages 1 to <12 years of age) with severe hemophilia A or B

Secondary Objectives:

• To characterize the safety and tolerability

• To determine fitusiran plasma concentrations at selected time points

Description:

The estimated total time on study is up to 256 weeks for participants who roll over into the extension study and up to 280 weeks for participants who do not roll over into the extension study (due to the requirement for up to an additional 6 months of follow-up for monitoring of AT levels).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: August 1, 2028
• Est. primary completion date: February 15, 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 1 Year to 11 Years

Eligibility

Inclusion Criteria:

• Male, aged 1 to <12 years at the time of enrollment.

• Severe hemophilia A or B (Factor VIII (FVIII) <1% or Factor IX (FIX) =2%)

• Participants must have inhibitory antibodies to FVIII or FIX and must meet one of the following Nijmegen-modified Bethesda assay results criteria:

• Inhibitor titer of =0.6 BU/mL at screening, OR

• Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of 2 consecutive titers =0.6 BU/mL, OR

• Inhibitor titer of <0.6 BU/mL at screening with medical record evidence of 1 inhibitor titer =0.6 BU/mL and a history of anamnestic response or severe allergic reaction (anaphylaxis or nephrotic syndrome)

• Adequate peripheral venous access, as determined by the Investigator, to allow the blood draws required by the study protocol

• Weight requirements at the time of enrollment: 8 to <45 kg

• Willing and able to comply with the study requirements and to provide signed written informed consent obtained from parent(s)/legal guardian (hereinafter the "parent") and written or oral assent obtained from participant, per local and national requirements

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• 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

• Acute or chronic Hepatitis B virus infection

• Acute Hepatitis A or hepatitis E infection

• HIV positive with a CD4 count of <400 cells/µL

• History of arterial or venous thromboembolism, unrelated to an indwelling venous access

• Inadequate renal function

• History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc)

• Subjects with central or peripheral indwelling catheters, with history of venous access complications leading to hospitalization and/or systemic anticoagulation therapy.

• History of intolerance to subcutaneous (SC) injection(s)

• Use of emicizumab (Hemlibra®) within 6 months prior to screening

• Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Drug:
• Fitusiran
Pharmaceutical form:Solution for injection-Route of administration:Subcutaneous

Locations

Country	Name	City	State
Canada	Investigational Site Number : 1240001	Hamilton	Ontario
Canada	Investigational Site Number : 1240002	Ottawa	Ontario
India	Investigational Site Number : 3560006	Bangalore
India	Investigational Site Number : 3560002	Mumbai
India	Investigational Site Number : 3560001	Pune-411011
India	Investigational Site Number : 3560004	Vellore
Italy	Investigational Site Number : 3800002	Firenze
Italy	Investigational Site Number : 3800001	Milano
Spain	Investigational Site Number : 7240002	Madrid	Madrid, Comunidad De
Turkey	Investigational Site Number : 7920001	Adana
Turkey	Investigational Site Number : 7920002	Istanbul
Turkey	Investigational Site Number : 7920003	Izmir
United States	University Hospitals of Cleveland Site Number : 8400007	Cleveland	Ohio
United States	Hackensack University Medical Center Site Number : 8400008	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center Site Number : 8400006	Hershey	Pennsylvania
United States	Children's Hospital Los Angeles Site Number : 8400002	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada,  India,  Italy,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma antithrombin (AT) activity levels	Characterize the AT activity at the optimal therapeutic dose	Day 1 to the AT analysis time point at the optimal therapeutic dose (approximately 256 weeks)
Secondary	Number of participants reported with adverse events	Number of participants reported with treatment-emergent adverse events (TEAEs)	Up to 280 weeks (up to 256 weeks of treatment + up to 24 weeks of AT follow up)
Secondary	Fitusiran plasma concentrations	Plasma samples will be collected for measurement of plasma concentrations of fitusiran at specific time points post dose on Day 1 and pre dose on Day 85	Day 1 and Day 85