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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02554773
Recruitment Status : Active, not recruiting
First Posted : September 18, 2015
Last Update Posted : October 26, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE September 15, 2015
First Posted Date  ICMJE September 18, 2015
Last Update Posted Date October 26, 2021
Actual Study Start Date  ICMJE September 18, 2015
Estimated Primary Completion Date October 20, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 25, 2021)
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [ Time Frame: Up to 7 years ]
Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
The long-term safety and tolerability of ALN-AT3SC evaluated by the proportion of patients experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation [ Time Frame: Through day 811 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2021)
  • Annualized bleed rate (ABR) [ Time Frame: Up to 7 years ]
  • Time intervals between bleeding episodes [ Time Frame: Up to 7 years ]
  • Weight-adjusted consumption of FVIII, FIX, or BPA [ Time Frame: 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 [ Time Frame: Up to 7 years ]
    QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL
  • Pharmacokinetics (PK) of fitusiran: Cmax [ Time Frame: Day 1, Month 12, Month 24 ]
  • Pharmacokinetics (PK) of fitusiran: AUC [ Time Frame: Day 1, Month 12, Month 24 ]
  • Pharmacokinetics (PK) of fitusiran: t1/2 [ Time Frame: Day 1, Month 12, Month 24 ]
  • Pharmacokinetics (PK) of fitusiran: CL/F [ Time Frame: Day 1, Month 12, Month 24 ]
  • Pharmacokinetics (PK) of fitusiran: V/F [ Time Frame: Day 1, Month 12, Month 24 ]
  • The effect of fitusiran on plasma levels of antithrombin (AT) and thrombin generation (TG) [ Time Frame: Up to 7 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
  • Change From Baseline in the Number of Bleeding Events [ Time Frame: Through day 811 ]
  • Change From Baseline in the Amount of Factor VIII (FVIII) or Factor IX (FIX) Administered for the Treatment of Bleeding Episodes (FVIII) or factor IX (FIX) and ALN-AT3SC for treatment of bleeding episodes [ Time Frame: Through day 811 ]
  • Number of Adverse Events in Patients Receiving Concomitantly Administered Factor VIII (FVIII) or Factor IX (FIX) and ALN-AT3SC [ Time Frame: Through day 811 ]
  • The assessment of changes in health-related quality of life (QOL) with long-term dosing of ALN-AT3SC [ Time Frame: Through day 751 ]
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    Cmax
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    tmax
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    AUC
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    t1/2
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    CL/F
  • Profile of Pharmacokinetics (PK) of ALN-AT3SC [ Time Frame: Through day 362 ]
    V/F
  • The effect of ALN-AT3SC on plasma levels of antithrombin (AT) and thrombin generation (TG) [ Time Frame: Through day 811 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hemophilia A
  • Hemophilia B
Intervention  ICMJE Drug: Fitusiran (SAR439774)
Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)
Study Arms  ICMJE Experimental: Fitusiran
Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.
Intervention: Drug: Fitusiran (SAR439774)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2016)
37
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2015)
30
Estimated Study Completion Date  ICMJE October 20, 2023
Estimated Primary Completion Date October 20, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Russian Federation,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02554773
Other Study ID Numbers  ICMJE LTE14762
ALN-AT3SC-002 ( Other Identifier: Alnylam )
2015-001395-21 ( EudraCT Number )
U1111-1251-5204 ( Registry Identifier: ICTRP )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations, MD Sanofi
PRS Account Sanofi
Verification Date October 25, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP