Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B (ATLAS-PEDS)

• ClinicalTrials.gov Identifier: NCT03974113
• Recruitment Status: Recruiting
• First Posted: June 4, 2019
• Last Update Posted: April 8, 2022
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

Brief 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 Objective:

• To characterize the safety and tolerability
• To determine fitusiran plasma concentrations at selected time points

Condition or disease	Intervention/treatment	Phase
Hemophilia	Drug: Fitusiran	Phase 2; Phase 3

Detailed Description:

The estimated total time on study is up to 160 weeks in participants who roll over into the extension study and up to 184 weeks in 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 28, 2020
• Estimated Primary Completion Date: August 9, 2023
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fitusiran; Participants will receive a selected dose of fitusiran on regular intervals, as per study protocol	Drug: Fitusiran; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Outcome Measures

Primary Outcome Measures :

1. Plasma antithrombin (AT) activity levels [ Time Frame: Day 1 to the AT analysis time point at the optimal therapeutic dose (approximately 160 weeks) ]
   Characterize the AT activity at the optimal therapeutic dose

Secondary Outcome Measures :

1. Number of participants reported with adverse events [ Time Frame: Up to 184 weeks (up to 160 weeks of treatment + up to 24 weeks of AT follow up) ]
   Number of participants reported with treatment-emergent adverse events (TEAEs)
2. Fitusiran plasma concentrations [ Time Frame: Day 1 and Day 85 ]
   Plasma samples will be collected for measurement of plasma concentrations of fitusiran at specific time points postdose on Day 1 and predose on Day 85

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 11 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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:

• 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)
• Participants 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)
• The 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.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext Option 6; Contact-US@sanofi.com

Locations

United States, California

Investigational Site Number 8400002; Recruiting

Los Angeles, California, United States, 90027

Investigational Site Number 8400010; Recruiting

Orange, California, United States, 92868

United States, New Jersey

Investigational Site Number 8400008; Recruiting

Hackensack, New Jersey, United States, 07601

United States, Ohio

Investigational Site Number 8400007; Recruiting

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Investigational Site Number 8400006; Completed

Hershey, Pennsylvania, United States, 17033

Canada

Investigational Site Number 1240001; Recruiting

Hamilton, Canada, L8N 3Z5

India

Investigational Site Number 3560001; Recruiting

Pune-411011, India, 411 011

Investigational Site Number 3560004; Recruiting

Vellore, India, 632004

Italy

Investigational Site Number 3800002; Recruiting

Firenze, Italy, 50134

Investigational Site Number 3800001; Recruiting

Milano, Italy, 20121

Spain

Investigational Site Number 7240002; Recruiting

Madrid, Spain, 28046

Turkey

Investigational Site Number 7920003; Recruiting

Bornova, Turkey, 35100

Investigational Site Number 7920002; Recruiting

Fatih, Turkey, 34093

Investigational Site Number 7920001; Recruiting

Seyhan, Turkey, 01130

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03974113
• Other Study ID Numbers: EFC15467; 2019-000679-18 ( EudraCT Number ); U1111-1223-4368 ( Other Identifier: UTN )
• First Posted: June 4, 2019
• Last Update Posted: April 8, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn