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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03417245




Registration number
NCT03417245
Ethics application status
Date submitted
25/01/2018
Date registered
31/01/2018

Titles & IDs
Public title
A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
Scientific title
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
Secondary ID [1] 0 0
ALN-AT3SC-004
Secondary ID [2] 0 0
EFC14769
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Hemophilia B 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 - factor concentrates

Experimental: Factor On-demand - Participants received on-demand factor concentrates (as needed, for episodic bleeding episodes, and not on a regular regimen intended to prevent spontaneous bleeding) per Investigator discretion for the treatment of breakthrough bleeding episodes from Day 1 up to a total of 9 months.

Experimental: Fitusiran 80 mg Prophylaxis - Participants received open-label fitusiran 80 milligram (mg) administered subcutaneously (SC) as prophylaxis once monthly from Day 1 up to a total of 9 months. Participants received on-demand factor concentrates (per investigator's discretion and within bleeding dosing guidelines) for the treatment of breakthrough bleeding episodes.


Treatment: Drugs: fitusiran
by SC injection

Treatment: Drugs: factor concentrates
by intravenous (IV) injection

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

Outcomes
Primary outcome [1] 0 0
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
Timepoint [1] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Primary outcome [2] 0 0
Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
Timepoint [2] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [1] 0 0
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period
Timepoint [1] 0 0
From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [2] 0 0
Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period
Timepoint [2] 0 0
From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [3] 0 0
Estimated Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period
Timepoint [3] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [4] 0 0
Observed Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period
Timepoint [4] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [5] 0 0
Estimated Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period
Timepoint [5] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [6] 0 0
Observed Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period
Timepoint [6] 0 0
From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcome [7] 0 0
Health-related Quality of Life (HRQOL): Change From Baseline in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score at Month 9
Timepoint [7] 0 0
Baseline (Day 1), Month 9
Secondary outcome [8] 0 0
Health-related Quality of Life (HRQOL): Change From Baseline in Haem-A-QOL Total Score at Month 9
Timepoint [8] 0 0
Baseline (Day 1), Month 9
Secondary outcome [9] 0 0
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Onset Period
Timepoint [9] 0 0
From Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was the earliest
Secondary outcome [10] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Timepoint [10] 0 0
From Baseline (Day 1) up to 15 months (i.e., 9 months treatment period + 6-month follow-up)

Eligibility
Key inclusion criteria
* Males, >=12 years of age.
* Severe hemophilia A or B without inhibitors.

* Severity confirmed by a central laboratory where FVIII level was less than (<) 1 percent (%) or Factor IX (FIX) level was less than or equal to (<=) 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 Bethesda units per milliliter (BU/mL) at Screening.
* No use of Bypassing agents 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 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, 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 hepatitis C virus infection.
* HIV positive with a cluster of differentiation-4 count of <200 cells/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 SC injection(s).
* Any other conditions or comorbidities that would make 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
Randomised controlled 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
Parallel
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 6101 - Camperdown
Recruitment hospital [2] 0 0
Investigational Site Number 6103 - Murdoch
Recruitment hospital [3] 0 0
Investigational Site Number 6104 - Prahran
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
6961 - Murdoch
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
China
State/province [9] 0 0
Guangzhou
Country [10] 0 0
China
State/province [10] 0 0
Hangzhou
Country [11] 0 0
China
State/province [11] 0 0
Shanghai
Country [12] 0 0
China
State/province [12] 0 0
Tianjin
Country [13] 0 0
Denmark
State/province [13] 0 0
Copenhagen
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Rouen
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Frankfurt Am Main
Country [19] 0 0
Germany
State/province [19] 0 0
Leipzig
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
India
State/province [21] 0 0
Bangalore
Country [22] 0 0
India
State/province [22] 0 0
Jaipur
Country [23] 0 0
India
State/province [23] 0 0
Lucknow
Country [24] 0 0
India
State/province [24] 0 0
Mumbai
Country [25] 0 0
India
State/province [25] 0 0
Pune
Country [26] 0 0
India
State/province [26] 0 0
Vellore
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat-Gan
Country [28] 0 0
Italy
State/province [28] 0 0
Padova
Country [29] 0 0
Japan
State/province [29] 0 0
Isehara
Country [30] 0 0
Japan
State/province [30] 0 0
Saitama
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Busan
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Daejeon
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Malaysia
State/province [34] 0 0
Ampang
Country [35] 0 0
Malaysia
State/province [35] 0 0
Johor Bahru
Country [36] 0 0
Malaysia
State/province [36] 0 0
Kota Kinabalu
Country [37] 0 0
South Africa
State/province [37] 0 0
Parktown
Country [38] 0 0
South Africa
State/province [38] 0 0
Port Elizabeth
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taichung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taoyuan
Country [43] 0 0
Turkey
State/province [43] 0 0
Adana
Country [44] 0 0
Turkey
State/province [44] 0 0
Antalya
Country [45] 0 0
Turkey
State/province [45] 0 0
Gaziantep
Country [46] 0 0
Turkey
State/province [46] 0 0
Istanbul
Country [47] 0 0
Turkey
State/province [47] 0 0
Izmir
Country [48] 0 0
Turkey
State/province [48] 0 0
Kayseri
Country [49] 0 0
Turkey
State/province [49] 0 0
Samsun
Country [50] 0 0
Ukraine
State/province [50] 0 0
Kyiv
Country [51] 0 0
Ukraine
State/province [51] 0 0
Lviv
Country [52] 0 0
Ukraine
State/province [52] 0 0
Mykolaiv
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Glasgow
Country [54] 0 0
United Kingdom
State/province [54] 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, MD
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.