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A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis (ATLAS-PPX)

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: NCT03549871
Recruitment Status : Active, not recruiting
First Posted : June 8, 2018
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE June 8, 2018
Last Update Posted Date March 29, 2021
Actual Study Start Date  ICMJE July 30, 2018
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
Annualized bleeding rate (ABR) [ Time Frame: 13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period) ]
Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period
Original Primary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
Annualized bleeding rate (ABR) [ Time Frame: 13 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2021)
  • Annualized spontaneous bleeding rate [ Time Frame: 13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period) ]
    Annualized spontaneous bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
  • Annualized joint bleeding rate [ Time Frame: 13 months (6 months in factor/BPA prophylaxis period and fitusiran baseline to end of study which includes one month onset period and 6 months efficacy period) ]
    Annualized joint bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
  • 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: 7 months ]
    Change in Haem-A-QOL physical health score and total score in the fitusiran treatment period
  • ABR in the onset period [ Time Frame: 1 months ]
    ABR in the fitusiran onset period
  • ABR in the treatment period [ Time Frame: 7 months ]
    ABR in the fitusiran treatment period
  • Annualized weight-adjusted consumption of factor/BPA [ Time Frame: 6 months ]
  • Number of patients reported with adverse events [ Time Frame: 13 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Annualized spontaneous bleeding rate [ Time Frame: 13 months ]
  • Annualized joint bleeding rate [ Time Frame: 13 months ]
  • 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: 13 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 in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
Official Title  ICMJE ATLAS-PPX: an Open-label, Multinational, Switching Study to Describe the Efficacy and Safety of Fitusiran Prophylaxis in Patients With Hemophilia A and B Previously Receiving Factor or Bypassing Agent Prophylaxis.
Brief Summary

Primary Objective:

To characterize the frequency of bleeding episodes while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor or bypassing agent (BPA) prophylaxis

Secondary Objectives:

  • To characterize the following while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis:
  • 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 characterize the frequency of bleeding episodes during the onset and treatment periods in patients receiving fitusiran
  • To characterize the safety and tolerability of fitusiran
  • Annualized weight-adjusted consumption of factor/BPA
Detailed Description

Study duration per participant is approximately 13 months including 6-Month factor or BPA prophylaxis period and 7-Month fitusiran treatment period. Study duration for patients in the subgroup of Cohort A is approximately 7 months corresponding to a 7-Month fitusiran treatment period.

Participants completing the treatment period will be proposed to enroll in an extension study

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia
Intervention  ICMJE Drug: Fitusiran
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Study Arms  ICMJE Experimental: Fitusiran
Fitusiran sub-cutaneous injection for 7 months
Intervention: Drug: Fitusiran
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
Actual Enrollment  ICMJE
 (submitted: February 1, 2021)
80
Original Estimated Enrollment  ICMJE
 (submitted: June 6, 2018)
30
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males, ≥12 years of age
  • Severe hemophilia A or B (as evidenced by a central laboratory measurement at screening or documented medical record evidence of FVIII <1% or FIX level ≤2%)
  • A minimum of 2 bleeding episodes requiring BPA treatment within the last 6 months prior to Screening for patients with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode requiring factor treatment within the last 12 months prior to Screening for patients without inhibitory antibodies to factor VIII or factor IX (Cohort B).
  • Must meet either the definition of inhibitor or non-inhibitor patient as below:
  • Inhibitor:Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to Screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria:
  • Inhibitor titer of ≥0.6 BU/mL at Screening, or
  • Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, or
  • Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of anamnestic response
  • The subgroup of patients in Cohort A patients must additionally meet the following criteria to be eligible to start treatment with fitusiran directly after the screening period:

    • Hemophilia B with inhibitory antibody to Factor IX as defined above
    • Not responding adequately to BPA treatment (historical ABR ≥20) prior to enrollment
    • In the opinion of the Investigator, with approval of Sponsor Medical Monitor, 6-month BPA prophylaxis period should be omitted.
  • Non-inhibitor:Use of factor concentrates for prophylaxis and for any 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 and
  • No use of bypassing agents to treat bleeding episodes for at least the last 6 months prior to Screening and
  • No history of immune tolerance induction therapy within the past 3 years prior to Screening.
  • Documented prophylactic treatment with factor concentrates or bypassing agents for the treatment of hemophilia A or B for at least 6 months prior to Screening
  • Adherent to the prescribed prophylactic therapy for at least 6 months prior to Screening per Investigator assessment
  • 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
  • AT activity <60% at Screening
  • Co-existing thrombophilic disorder
  • Clinically significant liver disease
  • Active Hepatitis C virus infection
  • Acute or chronic Hepatitis B virus 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,   Canada,   China,   Denmark,   France,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Germany,   South Africa,   Spain
 
Administrative Information
NCT Number  ICMJE NCT03549871
Other Study ID Numbers  ICMJE EFC15110
2016-004087-19 ( EudraCT Number )
ALN-AT3SC-009 ( Other Identifier: Alnylam )
U1111-1217-3270 ( Registry Identifier: WHO Universal Trial Number (UTN) )
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
Product Manufactured in and Exported from the U.S.: Yes
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 Sanofi
PRS Account Sanofi
Verification Date March 2021

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