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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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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

Conditions
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Hemophilia

Intervention / Treatment
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* Drug: Fitusiran


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fitusiran<br>Participants will receive a selected dose of fitusiran on regular intervals, as per study protocol | Drug: Fitusiran<br>* Pharmaceutical form:Solution for injection Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 160 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reported with adverse events | Number of participants reported with treatment-emergent adverse events (TEAEs) | Up to 184 weeks (up to 160 weeks of treatment + up to 24 weeks of AT follow up) | 
| Fitusiran plasma concentrations | 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 | Day 1 and Day 85 |