Brief Title
A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
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.
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
The estimated total time on study, inclusive of Screening, for each patient is up to 15
months for patients who enroll in the extension study except for patients in the subgroup of
Cohort A, which is up to 9 months. The estimated total time on study may be up to 21 months
(up to 15 months in patients in the subgroup of Cohort A) in patients who do not enroll in
the extension study due to the requirement for an additional up to 6 months of follow-up for
monitoring of AT levels.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Annualized bleeding rate (ABR)
Secondary Outcome
Annualized spontaneous bleeding rate
Condition
Hemophilia
Intervention
Fitusiran
Study Arms / Comparison Groups
Fitusiran
Description: Fitusiran sub-cutaneous injection for 7 months
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
80
Start Date
July 25, 2018
Completion Date
March 25, 2022
Primary Completion Date
January 20, 2022
Eligibility 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
Gender
Male
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Sciences & Operations, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03549871
Organization ID
EFC15110
Secondary IDs
2016-004087-19
Responsible Party
Sponsor
Study Sponsor
Genzyme, a Sanofi Company
Study Sponsor
Clinical Sciences & Operations, Study Director, Sanofi
Verification Date
April 2022