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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03549871




Registration number
NCT03549871
Ethics application status
Date submitted
25/05/2018
Date registered
8/06/2018

Titles & IDs
Public title
A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
Scientific 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.
Secondary ID [1] 0 0
2016-004087-19
Secondary ID [2] 0 0
EFC15110
Universal Trial Number (UTN)
Trial acronym
ATLAS-PPX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fitusiran
Treatment: Drugs - BPA prophylaxis
Treatment: Drugs - Factor (FVIII or FIX) prophylaxis

Experimental: Fitusiran - Cohort A \[inhibitor\]: participants with severe hemophilia A/B and inhibitory antibodies to coagulation factor VIII (FVIII)/factor IX (FIX) previously received BPA prophylaxis. Cohort B \[non-inhibitor\]: participants with severe hemophilia A/B without inhibitory antibodies to FVIII/FIX previously received factor prophylaxis. Participants from both cohorts was enrolled into 6-month factor/BPA prophylaxis period and continued their pre-study, regularly scheduled prophylaxis regimen with factor/BPAs. This period could be skipped by subgroup of Cohort A (hemophilia B with inhibitors to FIX and historical annualized bleeding rate \[ABR\] \>=20) that started directly with fitusiran. Post completing factor/BPA prophylaxis period, participants entered 7-month fitusiran treatment period (1-month onset+6-month efficacy) followed by AT follow-up/roll-over into LTE15174 (NCT03754790). Throughout study, participants could receive on-demand treatment for breakthrough BE with factor/BPAs, as appropriate.


Treatment: Drugs: Fitusiran
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Treatment: Drugs: BPA prophylaxis
Pharmaceutical form: solution for injection Route of administration: Intravenous

Treatment: Drugs: Factor (FVIII or FIX) prophylaxis
Pharmaceutical form: solution for injection Route of administration: Intravenous

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Estimated Annualized Bleeding Rate (ABR)
Timepoint [1] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Primary outcome [2] 0 0
Observed Annualized Bleeding Rate (ABR)
Timepoint [2] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [1] 0 0
Estimated Annualized Spontaneous Bleeding Rate
Timepoint [1] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [2] 0 0
Observed Annualized Spontaneous Bleeding Rate
Timepoint [2] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [3] 0 0
Estimated Annualized Joint Bleeding Rate
Timepoint [3] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [4] 0 0
Observed Annualized Joint Bleeding Rate
Timepoint [4] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [5] 0 0
Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Timepoint [5] 0 0
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Secondary outcome [6] 0 0
Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period
Timepoint [6] 0 0
Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period
Secondary outcome [7] 0 0
Estimated Annualized Bleeding Rate in the Fitusiran Onset Period
Timepoint [7] 0 0
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Secondary outcome [8] 0 0
Observed Annualized Bleeding Rate in the Fitusiran Onset Period
Timepoint [8] 0 0
Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest
Secondary outcome [9] 0 0
Estimated Annualized Bleeding Rate in the Fitusiran Treatment Period
Timepoint [9] 0 0
From Day 1 up to Day 190
Secondary outcome [10] 0 0
Observed Annualized Bleeding Rate in the Fitusiran Treatment Period
Timepoint [10] 0 0
from Day 1 up to Day 190
Secondary outcome [11] 0 0
Cohort A: Annualized Weight-adjusted Consumption of BPA (Activated Prothrombin Complex Concentrates)
Timepoint [11] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [12] 0 0
Cohort A: Annualized Weight-adjusted Consumption of BPA (Recombinant Factor VIIa)
Timepoint [12] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest
Secondary outcome [13] 0 0
Cohort B: Annualized Weight-adjusted Consumption of Factor
Timepoint [13] 0 0
Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest

Eligibility
Key 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 less than (<) 1 percent (%) or FIX level less than or equal to (<=) 2%).
* A minimum of 2 bleeding episodes required BPA treatment within the last 6 months prior to screening for participants with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode required factor treatment within the last 12 months prior to screening for participants without inhibitory antibodies to factor VIII or factor IX (Cohort B).
* Met either the definition of inhibitor or non-inhibitor participant as below:
* Inhibitor: Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met one of the following Nijmegen-modified Bethesda assay results criteria:
* Inhibitor titer of >=0.6 Bethesda Unit per milliliter (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 participants in Cohort A participants might 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 met each of the following criterion:
* Nijmegen-modified Bethesda assay inhibitor titer of <0.6 BU/mL at screening and
* No use of BPAs 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 BPAs 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.
* Willed and complied with the study requirements and to provide written informed consent and assent.
Minimum age
12 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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 per microliter.
* 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 subcutaneous injection(s).
* Any other conditions or comorbidities that made the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 6104 - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
China
State/province [2] 0 0
Beijing
Country [3] 0 0
Denmark
State/province [3] 0 0
Copenhagen
Country [4] 0 0
France
State/province [4] 0 0
Lyon
Country [5] 0 0
Ireland
State/province [5] 0 0
Crumlin
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat-Gan
Country [7] 0 0
Italy
State/province [7] 0 0
Milano
Country [8] 0 0
Japan
State/province [8] 0 0
Nagoya
Country [9] 0 0
Japan
State/province [9] 0 0
Nishinomiya
Country [10] 0 0
Japan
State/province [10] 0 0
Saitama
Country [11] 0 0
Japan
State/province [11] 0 0
Tokyo
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Busan
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Daejeon
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Malaysia
State/province [15] 0 0
Ampang
Country [16] 0 0
Malaysia
State/province [16] 0 0
Johor Bahru
Country [17] 0 0
Malaysia
State/province [17] 0 0
Kota Kinabalu
Country [18] 0 0
Mexico
State/province [18] 0 0
San Pablo
Country [19] 0 0
Turkey
State/province [19] 0 0
Adana
Country [20] 0 0
Turkey
State/province [20] 0 0
Ankara
Country [21] 0 0
Turkey
State/province [21] 0 0
Antalya
Country [22] 0 0
Turkey
State/province [22] 0 0
Gaziantep
Country [23] 0 0
Turkey
State/province [23] 0 0
Istanbul
Country [24] 0 0
Turkey
State/province [24] 0 0
Izmir
Country [25] 0 0
Turkey
State/province [25] 0 0
Kayseri
Country [26] 0 0
Turkey
State/province [26] 0 0
Samsun
Country [27] 0 0
Turkey
State/province [27] 0 0
Van
Country [28] 0 0
Ukraine
State/province [28] 0 0
Kyiv
Country [29] 0 0
Ukraine
State/province [29] 0 0
Lviv
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Glasgow
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.