Clinical trial NCT03974113: Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-06-04
Enrollment: 32
Sex: MALE
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 Objectives:

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

Detailed 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).

Eligibility 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:

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.

Primary outcomes:
measure: Plasma antithrombin (AT) activity levels
timeFrame: Day 1 to the AT analysis time point at the optimal therapeutic dose (approximately 256 weeks)
Secondary outcomes:
measure: Number of participants reported with adverse events
timeFrame: Up to 280 weeks (up to 256 weeks of treatment + up to 24 weeks of AT follow up)
measure: Fitusiran plasma concentrations
timeFrame: Day 1 and Day 85
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles Site Number : 8400002
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center Site Number : 8400008
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Site Number : 8400007
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center Site Number : 8400006
state: Pennsylvania
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Ottawa
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Bangalore
country: India
facility: Investigational Site Number : 3560006
city: Mumbai
country: India
facility: Investigational Site Number : 3560002
city: Pune-411011
country: India
facility: Investigational Site Number : 3560001
city: Vellore
country: India
facility: Investigational Site Number : 3560004
city: Firenze
country: Italy
facility: Investigational Site Number : 3800002
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
city: Madrid
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid, Comunidad De
city: Adana
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: