An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B

Sponsor

Genzyme, a Sanofi Company (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02554773

Collaborator

(none)

Enrollment

Locations

Arm

90.5

Anticipated Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B

Secondary Objectives:

To investigate the long-term efficacy of fitusiran
To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX (FIX) or bypassing agents (BPA) and fitusiran for treatment of bleeding episodes
To assess changes in health-related quality of life (QOL) over time
To characterize antithrombin (AT) reduction and thrombin generation (TG) increase
To characterize the pharmacokinetics (PK) of fitusiran

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A Hemophilia B	Drug: Fitusiran (SAR439774)	Phase 1/Phase 2

Detailed Description

It is anticipated that patients in this study will receive treatment with open label fitusiran for approximately 7 years or until fitusiran becomes commercially available, whichever occurs first.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Extension Study of Subcutaneously Administered Fitusiran in Patients With Moderate or Severe Hemophilia A or B Who Have Participated in a Previous Clinical Study With Fitusiran

Actual Study Start Date :

Sep 18, 2015

Anticipated Primary Completion Date :

Apr 4, 2023

Anticipated Study Completion Date :

Apr 4, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fitusiran Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.	Drug: Fitusiran (SAR439774) Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)

Arm

Intervention/Treatment

Experimental: Fitusiran

Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.

Drug: Fitusiran (SAR439774)

Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)

Outcome Measures

Primary Outcome Measures

Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [Up to 7 years]
Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation

Secondary Outcome Measures

Annualized bleed rate (ABR) [Up to 7 years]
Time intervals between bleeding episodes [Up to 7 years]
Weight-adjusted consumption of FVIII, FIX, or BPA [Up to 7 years]
BPA Assessment of concomitantly administered factor VIII (FVIII), factor IX (FIX), or bypassing agents (BPA) and fitusiran for treatment of bleeding
Changes in health-related quality of life (QOL) with long-term dosing of fitusiran [Up to 7 years]
QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL
Pharmacokinetics (PK) of fitusiran: Cmax [Day 1, Month 12, Month 24]
Pharmacokinetics (PK) of fitusiran: AUC [Day 1, Month 12, Month 24]
Pharmacokinetics (PK) of fitusiran: t1/2 [Day 1, Month 12, Month 24]
Pharmacokinetics (PK) of fitusiran: CL/F [Day 1, Month 12, Month 24]
Pharmacokinetics (PK) of fitusiran: V/F [Day 1, Month 12, Month 24]
The effect of fitusiran on plasma levels of antithrombin (AT) and thrombin generation (TG) [Up to 7 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Completed and tolerated study drug dosing in study TDR14767 (ALN-AT3SC-001)
Male aged ≥18 years
Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%
Willing and able to comply with the study requirements and provide written informed consent

Exclusion Criteria:

Clinically significant liver disease
Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/μL
History of venous thromboembolism
Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity
Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Ann Arbor	Michigan	United States	48109
2	Clinical Trial Site	Pittsburgh	Pennsylvania	United States
3	Clinical Trial Site	Plovdiv		Bulgaria
4	Clinical Trial Site	Sofia		Bulgaria
5	Clinical Trial Site	Kirov		Russian Federation
6	Clinical Trial Site	Moscow		Russian Federation
7	Clinical Trial Site	Zurich		Switzerland
8	Clinical Trial Site	Basingstoke		United Kingdom
9	Clinical Trial Site	Glasgow		United Kingdom
10	Clinical Trial Site	London		United Kingdom	NW3 2QG
11	Clinical Trial Site	London		United Kingdom	SW17 0QT
12	Clinical Trial Site	Truro		United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

Study Director: Clinical Sciences & Operations, MD, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genzyme, a Sanofi Company

ClinicalTrials.gov Identifier:

NCT02554773

Other Study ID Numbers:

LTE14762
ALN-AT3SC-002
2015-001395-21
U1111-1251-5204

First Posted:

Sep 18, 2015

Last Update Posted:

Aug 5, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Genzyme, a Sanofi Company

Hemophilia

RNAi therapeutic

Additional relevant MeSH terms:

Hemophilia A

Hemophilia B

Study Results

No Results Posted as of Aug 5, 2022