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A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors

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: NCT03417245
Recruitment Status : Active, not recruiting
First Posted : January 31, 2018
Last Update Posted : December 7, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE January 25, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date December 7, 2020
Actual Study Start Date  ICMJE March 1, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
Annualized bleeding rate (ABR) [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
Annualized bleeding rate (ABR) [ Time Frame: 9 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • Annualized bleeding rate (ABR) [ Time Frame: at 1 month (onset period) , 9 months (treatment period: 1 month onset period + efficacy period of 8 months) ]
  • Annualized spontaneous bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
  • Annualized joint bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
  • Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score on a scale of 0-100 with higher scores representing greater impairment [ Time Frame: 9 months (treatment period: 1 month onset period + efficacy period of 8 months) ]
  • Number of participants reported with treatment-emergent adverse events [ Time Frame: 15 months (9 months treatment + 6 months follow up) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
  • Annualized spontaneous bleeding rate [ Time Frame: 9 months ]
  • Annualized joint bleeding rate [ Time Frame: 9 months ]
  • Haem-A-QOL Questionnaire [ Time Frame: 9 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
Official Title  ICMJE ATLAS-A/B: A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients With Hemophilia A or B, Without Inhibitory Antibodies to Factor VIII or IX
Brief Summary

Primary Objective:

-To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by the frequency of bleeding episodes

Secondary Objectives:

  • To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by:

    • The frequency of spontaneous bleeding episodes
    • The frequency of joint bleeding episodes
    • Health-related quality of life (HRQOL) in patients ≥17 years of age
  • To determine the frequency of bleeding episodes during the onset period
  • To determine the safety and tolerability of fitusiran
Detailed Description

The duration of treatment with fitusiran is 9 months. The estimated total time on study, inclusive of Screening, for each patient is up to 11 months for all patients who enroll in the extension study and patients in the on-demand arm who do not enroll in the extension study. The estimated total time on the study may be up to 17 months in fitusiran treatment arm patients who do not enroll in the extension study due to the requirement for an additional 6 months of follow-up monitoring for antithrombin levels.

Patients who complete the study may be eligible for an open-label extension study LTE15174 (NCT03754790)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hemophilia A
  • Hemophilia B
Intervention  ICMJE
  • Drug: fitusiran
    by subcutaneous (SC) injection
  • Drug: factor concentrates
    by intravenous (IV) injection
Study Arms  ICMJE
  • Experimental: fitusiran
    Fitusiran administered subcutaneously (SC) as prophylaxis once monthly, with use of on-demand factor concentrates for treatment of breakthrough bleeding episodes. All patients will be treated for a total of 9 months
    Intervention: Drug: fitusiran
  • Experimental: On demand factor concentrates
    On-demand factor concentrates for treatment of breakthrough bleeding episodes. On-demand use of factor concentrates is defined as the use of these agents, as needed, for episodic bleeding, and not on a regular regimen intended to prevent spontaneous bleeding. All patients will be treated for a total of 9 months.
    Intervention: Drug: factor concentrates
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: January 30, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males, ≥12 years of age
  • Severe hemophilia A or B without inhibitors

    • Severity confirmed by a central laboratory where FVIII level is <1% or FIX level is ≤2% at Screening;
    • On-demand use of factor concentrate to manage bleeding episodes for at least the last 6 months prior to Screening, and meet each of the following criterion:

      • Nijmegen modified Bethesda assay inhibitor titer of <0.6 BU/mL at Screening
      • No use of BPAs to treat bleeding episodes for at least the last 6 months prior to Screening
      • No history of immune tolerance induction therapy within the last 3 years prior to Screening
  • A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to Screening.
  • Willing and able to comply with the study requirements and to provide written informed consent and assent

Exclusion Criteria:

  • Known co-existing bleeding disorders other than hemophilia A or B, i.e. Von Willebrand's disease, additional factor deficiencies, or platelet disorders
  • Antithrombin (AT) activity <60% at Screening
  • Co-existing thrombophilic disorder
  • Clinically significant liver disease
  • Active HCV infection
  • HIV positive with a CD4 count of <200 cells/μL
  • History of arterial or venous thromboembolism
  • Inadequate renal function
  • History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine (GalNAc)
  • History of intolerance to SC injection(s)
  • Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 12 Years and older   (Child, 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 Australia,   China,   Denmark,   France,   Germany,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   South Africa,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Bulgaria,   Portugal,   Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT03417245
Other Study ID Numbers  ICMJE EFC14769
ALN-AT3SC-004 ( Other Identifier: Alnylam )
2016-001464-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 December 2020

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