An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
Primary Purpose
Hemophilia A, Hemophilia B
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Fitusiran (SAR439774)
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A focused on measuring Hemophilia, RNAi therapeutic
Eligibility Criteria
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
Sites / Locations
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fitusiran
Arm Description
Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.
Outcomes
Primary Outcome Measures
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
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)
Time intervals between bleeding episodes
Weight-adjusted consumption of FVIII, FIX, or BPA
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
QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL
Pharmacokinetics (PK) of fitusiran: Cmax
Pharmacokinetics (PK) of fitusiran: AUC
Pharmacokinetics (PK) of fitusiran: t1/2
Pharmacokinetics (PK) of fitusiran: CL/F
Pharmacokinetics (PK) of fitusiran: V/F
The effect of fitusiran on plasma levels of antithrombin (AT) and thrombin generation (TG)
Full Information
NCT ID
NCT02554773
First Posted
September 15, 2015
Last Updated
April 3, 2023
Sponsor
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT02554773
Brief Title
An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 18, 2015 (Actual)
Primary Completion Date
March 21, 2023 (Actual)
Study Completion Date
March 21, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A, Hemophilia B
Keywords
Hemophilia, RNAi therapeutic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fitusiran
Arm Type
Experimental
Arm Description
Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.
Intervention Type
Drug
Intervention Name(s)
Fitusiran (SAR439774)
Intervention Description
Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)
Primary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Description
Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Time Frame
Up to 7 years
Secondary Outcome Measure Information:
Title
Annualized bleed rate (ABR)
Time Frame
Up to 7 years
Title
Time intervals between bleeding episodes
Time Frame
Up to 7 years
Title
Weight-adjusted consumption of FVIII, FIX, or BPA
Description
BPA Assessment of concomitantly administered factor VIII (FVIII), factor IX (FIX), or bypassing agents (BPA) and fitusiran for treatment of bleeding
Time Frame
Up to 7 years
Title
Changes in health-related quality of life (QOL) with long-term dosing of fitusiran
Description
QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL
Time Frame
Up to 7 years
Title
Pharmacokinetics (PK) of fitusiran: Cmax
Time Frame
Day 1, Month 12, Month 24
Title
Pharmacokinetics (PK) of fitusiran: AUC
Time Frame
Day 1, Month 12, Month 24
Title
Pharmacokinetics (PK) of fitusiran: t1/2
Time Frame
Day 1, Month 12, Month 24
Title
Pharmacokinetics (PK) of fitusiran: CL/F
Time Frame
Day 1, Month 12, Month 24
Title
Pharmacokinetics (PK) of fitusiran: V/F
Time Frame
Day 1, Month 12, Month 24
Title
The effect of fitusiran on plasma levels of antithrombin (AT) and thrombin generation (TG)
Time Frame
Up to 7 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations, MD
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Clinical Trial Site
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Clinical Trial Site
City
Plovdiv
Country
Bulgaria
Facility Name
Clinical Trial Site
City
Sofia
Country
Bulgaria
Facility Name
Clinical Trial Site
City
Kirov
Country
Russian Federation
Facility Name
Clinical Trial Site
City
Moscow
Country
Russian Federation
Facility Name
Clinical Trial Site
City
Zurich
Country
Switzerland
Facility Name
Clinical Trial Site
City
Basingstoke
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Glasgow
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Truro
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
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