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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genzyme Corp.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

28 Jul 2020 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-512501-76-00

EudraCT number

2019-000679-18

WHO UTN

U1111-1223-4368

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Pharmacodynamic, Efficacy, Therapy, Prophylaxis

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 2

1. To characterize the safety and tolerability
2. To determine fitusiran plasma concentrations at selected time points

Conditions and MedDRA coding

Hemophilia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001855-PIP01-15

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male, aged 1 to <12 years at the time of enrollment.
2. Severe hemophilia A or B (Factor VIII (FVIII) <1% or Factor IX (FIX) ≤2%)
3. 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)
4. Adequate peripheral venous access, as determined by the Investigator, to allow the blood draws required by the study protocol
5. Weight requirements at the time of enrollment: 8 to <45 kg
6. 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 15

1. Known co-existing bleeding disorders other than hemophilia A or B
2. Antithrombin (AT) activity <60% at Screening
3. Co-existing thrombophilic disorder
4. Clinically significant liver disease
5. Active Hepatitis C virus infection
6. Acute or chronic Hepatitis B virus infection
7. Acute Hepatitis A or hepatitis E infection
8. HIV positive with a CD4 count of <400 cells/μL
9. History of arterial or venous thromboembolism, unrelated to an indwelling venous access
10. Inadequate renal function
11. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc)
12. Subjects with central or peripheral indwelling catheters, with history of venous access complications leading to hospitalization and/or systemic anticoagulation therapy.
13. History of intolerance to subcutaneous (SC) injection(s)
14. Use of emicizumab (Hemlibra®) within 6 months prior to screening
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Plasma antithrombin (AT) activity levels

Secondary endpoints 2

1. Number of participants reported with adverse events
2. Fitusiran plasma concentrations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genzyme Corp.

Sponsor organisation

Genzyme Corp.

Address

450 Water Street

City

Cambridge

Postcode

02141-2288

Country

United States

Scientific contact point

Organisation

Genzyme Corp.

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Genzyme Corp.

Contact name

Global Regulatory Affairs

Third parties 12

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications