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CTRI Number  CTRI/2018/07/014698 [Registered on: 02/07/2018] Trial Registered Prospectively
Last Modified On: 27/05/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   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 
Scientific Title of Study   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 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
ALN-AT3SC-004 (Sanofi Genzyme EFC14769) Amndt 2dtd27Jun2018  Protocol Number 
NCT03417245  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Rashmi Chitgupi 
Designation  Associate Director - Clinical Management 
Affiliation  PPD Pharmaceutical Development India Private Limited 
Address  PPD Pharmaceutical Development India Private Limited. 101, A Wing, Fulcrum, Hiranandani Business Park
Sahar Road, Andheri East,
Mumbai
MAHARASHTRA
400099
India 
Phone  912266022900  
Fax  912266022999  
Email  Rashmi.Chitgupi@ppdi.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Rashmi Chitgupi 
Designation  Associate Director - Clinical Management 
Affiliation  PPD Pharmaceutical Development India Private Limited 
Address  PPD Pharmaceutical Development India Private Limited. 101, A Wing, Fulcrum, Hiranandani Business Park
Sahar Road, Andheri East,
Mumbai
MAHARASHTRA
400099
India 
Phone  912266022900  
Fax  912266022999  
Email  Rashmi.Chitgupi@ppdi.com  
 
Source of Monetary or Material Support
Modification(s)  
Sanofi Genzyme, 50 Binney Street, Cambridge, MA 02142, USA  
 
Primary Sponsor
Modification(s)  
Name  Sanofi Genzyme 
Address  50 Binney Street, Cambridge, MA 02142, USA 
Type of Sponsor  Other [Biotechnology Company] 
 
Details of Secondary Sponsor  
Name  Address 
PPD Pharmaceuticals India Private Limited  101, A Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East, Mumbai 400099, Maharashtra, India. 
 
Countries of Recruitment     Australia
Bulgaria
Canada
China
Denmark
France
Germany
Hungary
India
Ireland
Israel
Italy
Japan
Malaysia
Netherlands
Portugal
Republic of Korea
Russian Federation
South Africa
Spain
Taiwan
Turkey
Ukraine
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 8  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sonali Salvi  B. J. Medical College and Sassoon General Hospital  3rd Floor, Department of Medicine,Jai Prakash Narayan Road Pune Railway Station, Pune, Maharashtra 411001, India
Pune
MAHARASHTRA 		 919422508154

sonalionly@gmail.com 
Dr Upendra Sharma  Bhagwan Mahaveer Cancer Hospital and Research Centre  Room no 513, Jawahar Lal Nehru Marg, Jaipur, 302017, Rajasthan, India
Jaipur
RAJASTHAN 		 919413964612

drupendra.sharma@yahoo.co.in 
Dr Alok Srivastava  Christian Medical College  Room no 2, Department Of Neurological Sciences Vellore, Tamil Nadu 632004, India
Vellore
TAMIL NADU 		 914162282352

aloks@cmcvellore.ac.in 
Dr Savita Rangarajan  K J Somaiya Hospital and Research Centre  Somaiya Ayurvihar, Eastern Express Highway, Sion East Pin Code - 400022
Mumbai
MAHARASHTRA 		 919619525341

rangarajansavita@gmail.com 
Dr Shailendra Prasad Verma  King George Medical University  Room no 505, 5th floor, Chowk Erstwhile Chhatrapati Shahuji Maharaj Medical University Lucknow, 226003, India
Lucknow
UTTAR PRADESH 		 919451475843

drspkgmu@rediffmail.com 
Dr Shashikant Apte  Sahyadri Super Specialty Hospital  30C, Karve road, Erandwane, Pune – 411004, Maharashtra, India
Mumbai
MAHARASHTRA 		 919822404983
912025459117
shashikant.apte@gmail.com 
Dr Chandrakala Shanmukhaiah  Seth G S Medical College and K.E.M Hospital  Acharya Dhonde Marg, Department of Hematology, 10th floor, New building, Mumbai, Maharashtra - 400012, India
Mumbai
MAHARASHTRA 		 919699087654

drchandra1s@gmail.com 
Dr Ross Cecil Reuben  St Johns Medical College Hospital  54A, Ground floor, Sarjapur Road, Bangalore, Karnataka 560034, India
Bangalore
KARNATAKA 		 919448493705

cecil.ross@bsnl.co.in 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 8  
Name of Committee  Approval Status 
Ethics Committee Silver  Approved 
Institutional Ethics Committee  Approved 
Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital and Research Centre  Approved 
Institutional Ethics Committee of B. J. Government Medical College and Sassoon General Hospital  Approved 
Institutional Ethics Committee, St.Johns Medical College  Approved 
Institutional Ethics Committee-II, Seth G S Medical College and K.E.M Hospital  Approved 
K J Somaiya Medical College and Research Centre  Approved 
Sahyadri Hospital Limited Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Hemophilia A Hemophilia B ,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Fitusiran (SAR439774 [formerly Alnylam ALN-AT3SC])  In Fitusiran treatment arm: Fitusiran 80 mg administered subcutaneously as prophylaxis once monthly, with use of on demand factor concentrates for treatment of breakthrough bleeding episodes 
Comparator Agent  On-demand Factor VIII or IX  In On-demand factor concentrates for treatment of breakthrough bleeding episodes 
 
Inclusion Criteria  
Age From  12.00 Year(s)
Age To  99.00 Year(s)
Gender  Male 
Details  1) Males, ≥12 years of age

2) Severe hemophilia A or B without inhibitors evidenced by:
a. A central laboratory measurement or documented medical record evidence of
FVIII <1% or FIX level ≤2% at Screening.
b. On-demand use of factor concentrate to manage bleeding episodes for at least the last
6 months prior to Screening

3) A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to Screening.


4) Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of patients under the age of legal consent, per local and
national requirements. 
 
ExclusionCriteria 
Details  1. Known co-existing bleeding disorders other than hemophilia A or B, ie, Von
Willebrand’s disease, additional factor deficiencies, or platelet disorders.
2. Current use of factor concentrates as regularly administered prophylaxis designed to
prevent spontaneous bleeding episodes.
3. AT activity <60% at Screening as determined by central laboratory measurement.
4. Presence of clinically significant liver disease, or as indicated by any of the conditions
below:
a. INR >1.2;
b. ALT and/or AST >1.5× upper limit of normal reference range (ULN);
c. Total bilirubin >ULN (>1.5 ULN in patients with Gilbert’s Syndrome);
d. History of portal hypertension, esophageal varices, or hepatic encephalopathy;
e. Presence of ascites by physical exam
5. Hepatitis C virus antibody positive, except patients with a history of HCV infection who
meet both conditions a. and b.:
a. Completed curative treatment at least 12 weeks prior to enrollment and attained
sustained virologic response as documented by a negative HCV RNA at screening, or
they have spontaneously cleared infection as documented by negative HCV RNA at
Screening.
b. No evidence of cirrhosis
6. Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
7. Presence of acute or chronic hepatitis B infection (IgM anti-HBc antibody positive or
HBsAg positive).
8. Platelet count ≤100,000/μL.
9. Presence of acute infection at Screening.
10. Known to be HIV positive with CD4 count <200 cells/μL.
11. Estimated glomerular filtration rate ≤45 mL/min/1.73m2 (using the Modification of Diet
in Renal Disease [MDRD] formula).
12. Co-existing thrombophilic disorder, as determined by presence of any of the below as
identified at central laboratory (or via historical results, where available):
a. FV Leiden (homozygous or heterozygous)
b. Protein S deficiency
c. Protein C deficiency
d. Prothrombin mutation (G20210A; homozygous or heterozygous)
13. History of antiphospholipid antibody syndrome.
14. History of arterial or venous thromboembolism, atrial fibrillation, significant valvular
disease, myocardial infarction, angina, transient ischemic attack, or stroke. Patients who
have experienced thrombosis associated with indwelling venous access may be enrolled.
15. Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin
that has been successfully treated.
16. Any condition (eg, medical concern), which in the opinion of the Investigator, would
make the patient unsuitable for dosing on Day 1 or which could interfere with the study
compliance, the patient’s safety and/or the patient’s participation in the completion of the
treatment period of the study. This includes significant active and poorly controlled
(unstable) cardiovascular, neurologic, gastrointestinal, endocrine, renal or psychiatric
disorders unrelated to hemophilia identified by key laboratory abnormalities or medical
history.
17. At Screening, anticipated need of surgery during the study or planned surgery scheduled
to occur during the study.
18. Completion of a surgical procedure within 14 days prior to Screening, or currently
receiving additional factor infusion for postoperative hemostasis.
19. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or
GalNAc.
20. Inadequate venous access, as determined by the Investigator, to allow the blood draws
required by the study protocol.
21. History of intolerance to SC injection(s).
22. Current or future participation in another clinical study, scheduled to occur during this
study, involving an investigational product other than fitusiran or investigational device;
in order to participate in this study, patient must discontinue the investigational product at
least 30 days (or 5× the investigational product half-life, whichever is longer) prior to
dosing (Day 1).
23. Current or prior participation in a gene therapy trial.
24. History of alcohol abuse within the 12 months before Screening.  
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Annualized bleeding rate (ABR)   Annualized bleeding rate (ABR) : 9 months 
 
Secondary Outcome  
Outcome  TimePoints 
1. Annualized spontaneous bleeding rate

2. Annualized joint bleeding rate

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
 		 9 months
9 months
9 months 
 
Target Sample Size   Total Sample Size="120"
Sample Size from India="9" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   30/08/2018 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  30/04/2018 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="9"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Closed to Recruitment of Participants 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details
Modification(s)  		 Not Applicable 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  		 The purpose of this study is to determine the frequency of bleeding episodes in adult and adolescent patients receiving fitusiran as prophylactic treatment of hemophilia compared with patients who are assigned to continue with their regular medication. In addition, the study will assess safety, quality of life, pharmacodynamics (PD), and pharmacokinetics (PK). 
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