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CTRI Number  CTRI/2024/06/068588 [Registered on: 07/06/2024] Trial Registered Prospectively
Last Modified On: 17/09/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Study to Compare the Efficacy and Safety of Luspatercept vs Epoetin Alfa for the Treatment of Anemia Myelodysplastic Syndrome  
Scientific Title of Study   A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) vs Epoetin Alfa for the Treatment of Anemia Due to Revised International Prognostic Scoring System (IPSS-R) Very Low, Low, or Intermediate-Risk Myelodysplastic Syndrome (MDS) in Erythropoiesis-stimulating Agent (ESA)-naive Participants who are Non-Transfusion Dependent (NTD) 
Trial Acronym  ELEMENT-MDS 
Secondary IDs if Any  
Secondary ID  Identifier 
2022-500430-29-00  EudraCT 
NCT05949684  ClinicalTrials.gov 
Protocol no CA056-025, Version no 2.0 dated 30 Aug 2023  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Shilpi Sinha 
Designation  Associate Director, Country Head RCO India 
Affiliation  Bristol Myers Squibb India Pvt. Ltd. 
Address  Bristol Myers Squibb India Pvt. Ltd One international Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India
Mumbai
MAHARASHTRA
400013
India 
Phone  02266288600  
Fax    
Email  Shilpi.Sinha@bms.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Kartik Doshi 
Designation  Associate Director, Medical India 
Affiliation  Bristol Myers Squibb India Pvt. Ltd. 
Address  Bristol Myers Squibb India Pvt. Ltd One international Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India
Mumbai
MAHARASHTRA
400013
India 
Phone  02266288600  
Fax    
Email  Kartik.Doshi@bms.com  
 
Details of Contact Person
Public Query  
Name  Dr Kartik Doshi 
Designation  Associate Director, Medical India 
Affiliation  Bristol Myers Squibb India Pvt. Ltd. 
Address  Bristol Myers Squibb India Pvt. Ltd One international Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India

MAHARASHTRA
400013
India 
Phone  02266288600  
Fax    
Email  Kartik.Doshi@bms.com  
 
Source of Monetary or Material Support
Modification(s)  
Bristol Myers Squibb India Private Limited One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India  
 
Primary Sponsor  
Name  Bristol Myers Squibb India Private Limited 
Address  One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Australia
Brazil
Canada
China
Colombia
Czech Republic
France
Germany
Greece
Hungary
India
Italy
Japan
Mexico
Poland
Spain
United States of America  
Sites of Study
Modification(s)  
No of Sites = 6  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Tulika Seth  All India Institutes of Medical Sciences  5th floor, Teaching block floor, Room no-5017, New Delhi - 110029
New Delhi
DELHI 		 09811262092

drtulikaseth@gmail.com 
Dr Pavan Kumar Boyella   Basavatarakam Indo American Hospital  Road no. 10, Banjara Hills, Hyderabad - 500034
Hyderabad
TELANGANA 		 09656100255

drboyellapk@gmail.com 
Dr Sachin Suresh Jadhav  Healthcare Global Hospital  Haematology Department, 4th Floor, Tower-1, P. kalingarao Road, Sampangiram nagar, Bangalore – 560027
Bangalore
KARNATAKA 		 0846607700

drsachinjadhav@hotmail.com 
Dr Sandip Abhaykumar Shah  Hemato Oncology Clinic Ahmedabad Pvt Ltd  Hemato Oncology Clinic Ahmedabad Pvt Ltd, “Vedanta” Institute of Medical Science, Ground floor & first floor, Near Samved hospital, Navrangpura, Ahmedabad- 380009, Gujarat, India
Ahmadabad
GUJARAT 		 09824041170

sandip60@yahoo.com 
Dr Samal Priyanka  Institute of Medical Sciences and Sum Hospital  2nd floor, Shiksha "O" Anusandhan University, Hemato-oncology Department, Bhubaneswar - 751003
Cuttack
ORISSA 		 06742386281

samalpriyanka80@gmail.com 
Dr Dinesh Bhurani  Rajiv Gandhi Cancer Institute and Research Centre  Rajiv Gandhi Cancer Institute and Research Centre, Room No 3265, Department of Hematology, Sir Chotu Ram Marg, Rohini Institutional Area, Sector 5, Rohini, New Delhi - 110085, India
New Delhi
DELHI 		 09971500861

bhurani@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Ethics Committee of CIMS  Approved 
IEC IMS and SUM Hospital  Approved 
Institutional Ethics Committee - All India Institute of Medical Sciences  Approved 
Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Centre  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D758||Other specified diseases of bloodand blood-forming organs,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Comparator Agent  Epoetin alfa (Procrit/ Binocrit)   Dose levels are as follows SC injection: a) 2,000 IU in 1.0mL b) 4,000 IU in 0.4 mL c) 6,000 IU in 0.6 mL d) 20,000 IU in 0.5 mL e) 30,000 IU in 0.75 mL f) 40,000 IU in 1.0 mL Initial dose level is 450 IU/kg QW (maximum total starting dose is 40,000 IU) Titration may occur up to 1,050 IU/kg and down to 337.5IU/kg  
Intervention  Luspatercept (BMS-986346/ACE-536)   Dose levels: 25 mg and75 mg glass vials Initial dose level is 1.0mg/kg SC injection Q3W Titration may occur up to 1.75mg/kg and down to 0.45mg/kg  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1) Males and females ≥ 18 years of age (or local age of consent) at the time of signing the informed consent.
2) Participant has documented diagnosis of MDS according to World Health Organization (WHO) 2016 that meet IPSS-R classification of very low, low, or intermediate-risk disease, (Intermediate-risk of less than 3.5 IPSS-R score) confirmed via bone marrow aspirate and:
a) less than 5 percentage blasts in bone marrow and less than 1 percentage blasts in peripheral blood
3) Participant has a baseline endogenous serum erythropoietin level of less than 500 UL.
4) Participant must be transfusion independent, according to IWG 2018 criteria as documented by the following criteria
a) Received no RBC transfusions within 16 weeks prior to randomization
5) Participant has a mean baseline Hb concentration prior to randomization of less than or equal to 9.5 g per dL. Mean Hb is defined as the mean of all central or local or pre-transfusion available Hb measurements during the 16 weeks prior to randomization (with a minimum of 2 measurements at least 1 week apart). Only Hb levels greater than 21 days following a transfusion are acceptable. The last measurement must be within 35 days of randomization
6) Participant has symptom(s) of anemia
a) Participant records a severity score of moderate or greater on at least 1 PGI-S item of
fatigue, weakness, shortness of breath, or dizziness performed during the screening period
7) Participant has Eastern Cooperative Oncology Group score of 0, 1, or 2
8) Participant must be Erythropoiesis-stimulating agent (ESA) Naive. Prior treatment with epoetin alfa or epoetin biosimilars, or darbepoetin alfa, is not acceptable for entry into the study
 
 
ExclusionCriteria 
Details  1)Participant with MDS associated with del (5q) cytogenetic abnormality or MDS unclassifiable (MDS-U) according to WHO 2016 classification
2)Participant with myelodysplastic or myeloproliferative neoplasms (MDS or MPN) according to WHO 2016 classification that is chronic myelomonocytic leukemia, Atypical chronic myeloid leukemia, BCR-ABL12, juvenile myelomonocytic leukemia, MDS or MPN unclassifiable)
3) Participant with secondary MDS (MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and or radiation for other diseases)
4) Participant with known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia (Example- severe G6PD deficiency, pyruvate kinase deficiency, etc), or hypothyroidism, or any type of known clinically significant bleeding or sequestration. Participant with drug induced anemia (Example - mycophenolate).
a) Iron deficiency to be determined by serum ferritin less than 100 ug per L and additional testing if clinically indicated (Example - calculated transferrin saturation [iron or total iron binding capacity less than or equal to 20 percentage] or bone marrow aspirate stain for iron).
5)Bleeding disorders manifested by frequent bleeding episodes (Example - menorrhagia, epistaxis, clotting disorders)
6)Participant with known history of diagnosis of acute myeloid leukemia
7)Uncontrolled hypertension defined as repeated elevations of systolic blood pressure of greater than or equal to 140 mmHg and or diastolic blood pressure greater than or equal to 90 mmHg despite adequate treatment or with a history of hypertensive crisis or hypertensive encephalopathy 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To compare the proportion of participants with lower-risk NTD MDS who convert to TD (≥3 RBC units/16weeks based on IWG 2018)70between luspatercept vs epoetin alfa   Week 1 through Week 96 
 
Secondary Outcome  
Outcome  TimePoints 
To compare the erythroid response of luspatercept vs epoetin alfa in participants with lower-risk NTD MDS based on IWG 2018  Week 1 through Week 48 
To further compare the erythroid response with luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Week 1 through Week 48
Week 49through Week 96
Week 1 through Week 96 
To further compare the proportion of participants with lower-risk NTD MDS who convert to TD (≥3 RBC units/16 weeks based on IWG 201870) between luspatercept vs epoetin alfa   Week 1 through Week 48 
To evaluate whether luspatercept reduces the risk of conversion to transfusion dependence (TD) in participants with lower-risk NTD MDS based on IWG 2018  Week 1 through EOS 
Transfusion-free survival
 		 Week 1 through EOS 
To further compare the RBC transfusion burden effect of luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Week 1 through Week 48
Week 1 through Week 96
Week 1 through EOS  
To assess the effect of luspatercept vs epoetin alfa on HRQoL in participants with lower-risk NTD MDS   Screening through 42 days post last dose
Screening through EOS 
To characterize the safety and immunogenicity of luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Screening through 42 days post last dose
W1D1 through Week 96 
To characterize the PK of luspatercept in participants with lower-risk NTD MDS  W1D1 through Week 96 
To compare the neutrophil and platelet response with luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Week 1 through Week 24
Week 1 through Week 48
Week 1 through Week 96 
To compare the rates of progression to high-risk MDS and AML with luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Randomization through EOS  
To compare overall survival with luspatercept vs epoetin alfa in participants with lower-risk NTD MDS  Randomization through EOS 
Duration of mHI-E  Week 1 through EOT 
Time to mHI-E  Week 1 through Week 48
Week 1 through Week 96
 
RBC TI for > 24 weeks  Week 1 through Week 48
Week 1 through Week 96
Week 1 through EOS
 
 
Target Sample Size   Total Sample Size="360"
Sample Size from India="12" 
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)   01/07/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  24/10/2023 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="5"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary  

This is a global Phase 3, open-label, randomized multicenter study to compare the efficacy and safety of luspatercept (BMS-986346/ACE-536) versus epoetin alfa in the treatment of anemia in adults due to IPSS-R very low, low, or intermediate-risk MDS in ESA-naive participants who are NTD. The study for each participant will include a Screening Period of 5 weeks (35 days), a Treatment Period of 96 weeks, an Extension Phase, and a Post Treatment Follow-up Period (PTFP) for approximately 5 years from first dose of the investigational product (IP) or approximately 3 years from last dose (whichever occurs later). The Extension Phase, and/or PTFP may be completed during this study or a rollover protocol for continued access to IP and to evaluate long-term safety of participants. 

 
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