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Fitusiran prophylaxis in male pediatric subjects aged 1 to less than 12 years with hemophilia A or B

Phase 1
Conditions
MedDRA version: 20.0Level: LLTClassification code 10066439Term: HemophiliaSystem Organ Class: 100000004850
Hemophilia A or B
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2019-000679-18-IT
Lead Sponsor
GENZYME CORPORATIO
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Male
Target Recruitment
12
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) - 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 anamnestic response.
- 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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)
- 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)
- 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main 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<br>- To characterize the pharmacokinetics (PK)<br>;Primary end point(s): Lowering of plasma antithrombin (AT) activity level; Lowering of plasma antithrombin (AT) activity level from Day 1 pre-fitusiran dose to Day 85;Timepoint(s) of evaluation of this end point: Day 1 to Day 85
Secondary Outcome Measures
NameTimeMethod
Timepoint(s) of evaluation of this end point: 1 : 160 weeks<br>2, 3, 4 : Day 1, Day 29, Day 57;Secondary end point(s): 1 - Number of participants reported with adverse events; Number of participants reported with treatment-emergent adverse events (TEAEs) <br>2 - Pharmacokinetics (PK): Maximum plasma concentration (Cmax); Plasma samples will be collected for measurement of plasma concentrations of fitusiran such as Cmax. <br>3 - Pharmacokinetics (PK): Time to reach maximum plasma concentration (Tmax); To evaluate time to reach Cmax<br>4 - Pharmacokinetics (PK): Ctrough; To evaluate concentration observed just before investigational medicinal product (IMP) administration during repeated dosing (Ctrough)
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