A study to test a medicine (fitusiran) injected under the skin for preventing bleeding episodes in male adolescent or adult participants with severe Hemophilia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

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

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Jul 2023 → ongoing

Decision date (initial)

2023-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

sanofi research & development

External identifiers

EU CT number

2022-500221-33-01

WHO UTN

U1111-1275-9584

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Prophylaxis, Efficacy

To characterize the frequency of treated bleeding episodes while receiving fitusiran prophylaxis

Secondary objectives 6

1. (Key) To evaluate the efficacy of fitusiran prophylaxis treatment compared to prophylaxis standard of care (SOC)
2. (Key) To evaluate the efficacy of fitusiran prophylaxis treatment compared to on-demand SOC
3. To characterize the following while receiving fitusiran prophylaxis, relative to receiving SOC: the frequency of treated spontaneous bleeding episodes, the frequency of treated joint bleeding episodes, health related quality of life (HRQOL) in participants ≥17 years of age
4. To characterize the frequency of treated bleeding episodes during the 18-month efficacy period and 36-month treatment period in participants receiving fitusiran
5. To characterize the annualized weight-adjusted consumption of clotting factor concentrates/ bypassing agents (CFC/BPA)
6. To characterize the safety and tolerability of fitusiran

Conditions and MedDRA coding

Hemophilia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Diagnosis of severe congenital hemophilia A or B (FVIII <1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
2. For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
3. Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements

Exclusion criteria 16

1. Known co-existing bleeding disorders other than congenital hemophilia A or B
2. History of arterial or venous thromboembolism, not associated with an indwelling venous access
3. History of intolerance to SC injection(s).
4. Current participation in immune tolerance induction therapy (ITI)
5. Prior gene therapy
6. Current or prior participation in a fitusiran trial
7. Current or prior participation in a gene therapy trial
8. Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
9. Presence of clinically significant liver disease
10. AT activity <60% at Screening
11. Co-existing thrombophilic disorder
12. Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
13. Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
14. Presence of acute or chronic hepatitis B infection
15. Known to be HIV positive with CD4 count <200 cells/μL.
16. Reduced renal function

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized Bleeding Rate (ABR) in the fitusiran primary efficacy period

Secondary endpoints 9

1. Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on prophylaxis standard of care (SOC) in the SOC period
2. Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on on-demand standard of care (SOC) in the SOC period
3. Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC period
4. Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC period
5. Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis
6. Annualized bleeding rate (ABR) in the fitusiran 18-month efficacy period
7. Annualized bleeding rate (ABR) in the fitusiran 36-month treatment period
8. Annualized weight-adjusted consumption of CFC/BPA
9. Number of participants with adverse events

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 25

Locations

6 EU/EEA countries · 18 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 143 files

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

Application history

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