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

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ClinicalTrials.gov Identifier: NCT03549871
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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 period in patients receiving fitusiran
  • To characterize the safety and tolerability of fitusiran
  • Annualized weight-adjusted consumption of factor/BPA

Condition or disease Intervention/treatment Phase
Hemophilia Drug: Fitusiran Phase 3

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : July 30, 2018
Estimated Primary Completion Date : June 29, 2021
Estimated Study Completion Date : June 29, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Experimental: Fitusiran
Fitusiran fixed dose, once-monthly sub-cutaneous injection for 7 months
Drug: Fitusiran
Pharmaceutical form: solution for injection Route of administration: subcutaneous




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. ABR in the onset period [ Time Frame: 1 months ]
    ABR in the fitusiran onset period

  5. ABR in the treatment period [ Time Frame: 7 months ]
    ABR in the fitusiran treatment period



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03549871


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

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Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03549871     History of Changes
Other Study ID Numbers: EFC15110
2016-004087-19 ( EudraCT Number )
ALN-AT3SC-009 ( Other Identifier: Alnylam )
U1111-1217-3270 ( Registry Identifier: WHO Universal Trial Number (UTN) )
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
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/

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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

Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants