Long-term Safety and Efficacy Study of Fitusiran in Patients with Hemophilia A or B, with or without Inhibitory Antibodies to Factor VIII or IX

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genzyme Corp.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male

Therapeutic area

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

Trial duration

3 Jun 2024 → 17 Nov 2025

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2023-508884-59-00

EudraCT number

2018-002880-25

WHO UTN

U1111-1210-0018

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Prophylaxis, Therapy, Efficacy, Safety

To characterize the long-term safety and tolerability of
fitusiran

Secondary objectives 2

1. 1. To characterize the efficacy and long-term efficacy of fitusiran as assessed by the frequency of: • Bleeding episodes • Spontaneous bleeding episodes • Joint bleeding episodes
2. 2. To characterize the effects of fitusiran on health-related quality of life measures in participants ≥17 years of age

Conditions and MedDRA coding

Hemophilia A or Hemophilia B

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 01. Participant must be at least 12 years of age inclusive, at the time of signing the informed consent
2. 02. Participants with severe hemophilia A or B who have completed a Phase 3 fitusiran clinical trial
3. 03. Male
4. 04. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. In countries where legal age of majority is above 18 years,a specific ICF must also be signed by the participant's legally authorized representative.

Exclusion criteria 7

1. 01. Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional factor concentrate or BPA infusion for postoperative hemostasis
2. 02. Current participation in tolerance induction treatment (ITI)
3. 03. Current use of factor concentrates or BPAs as regularly administered prophylaxis designed to prevent spontaneous bleeding episodes. However, participants requiring factor concentrates or BPAs prophylaxis during the study dosing pause period
4. 04. Use of compounds other than factor concentrates or BPAs for hemophilia treatment
5. 05. Current or prior participation in a gene therapy trial
6. 06. ALT and/or AST >1.5× upper limit of normal reference range (ULN) for patients who are naïve to fitusiran at study start; ALT and/or AST >5× ULN for patients who were in the fitusiran arm in the parent study.
7. 07Additional exclusions for participants not currently participating in a fitusiran trial at the time of enrollment in the lower dose cohort: ​ - Clinically significant liver disease ​ - History of arterial or venous thromboembolism​​

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ​​Number of participants with treatment emergent adverse events (TEAEs)​

Secondary endpoints 4

1. Annualized bleeding rate in the treatment period.
2. Annualized spontaneous bleeding rate in the treatment period.
3. Annualized joint bleeding rate in the treatment period.
4. Change in haemophilia quality of life questionnaire for adults (HaemAQoL) physical health score in the treatment period (in participants ≥17 years of age).

Investigational products

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

Test 1

Auxiliary 5

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 10

Locations

5 EU/EEA countries · 8 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 26 files

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

Application history

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