Hemophilia
Conditions
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).
Interventions
DRUGFitusiran
Pharmaceutical form:Solution for injection-Route of administration:Subcutaneous
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
1 Years to 11 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma antithrombin (AT) activity levels | Day 1 to the AT analysis time point at the optimal therapeutic dose (approximately 256 weeks) | Characterize the AT activity at the optimal therapeutic dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants reported with adverse events | Up to 280 weeks (up to 256 weeks of treatment + up to 24 weeks of AT follow up) | Number of participants reported with treatment-emergent adverse events (TEAEs) |
| Fitusiran plasma concentrations | Day 1 and Day 85 | 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 |
Countries
Canada, India, Italy, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed