ELEMENT-MDS: A Study to Compare the Efficacy and Safety of Luspatercept in Participants With Myelodysplastic Syndrome (MDS) and Anemia Not Receiving Blood Transfusions (ELEMENT-MDS)

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): The "ELEMENT-MDS" Trial

The purpose of the study is to compare the efficacy and safety of Luspatercept vs epoetin alfa in the treatment of anemia in adults due to IPSS-R very low, low, intermediate-risk MDS in ESA-naïve participants who are non-transfusion dependent (NTD).

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Biological: Luspatercept; Biological: Epoetin Alfa

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, CP1280AEB
    • Local Institution - 0012
  • Buenos Aires, Argentina, C1425DND
    • Local Institution - 0010
  • Buenos Aires, Argentina, C1426ANZ
    • Local Institution - 0009
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Local Institution - 0071
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution - 0113
    • Coffs Harbour, New South Wales, Australia, 2450
      • Local Institution - 0254
  • Queensland
    • Gold Coast, Queensland, Australia, 4217
      • Local Institution - 0246
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0054
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0052
• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Local Institution - 0056
  • São Paulo, Brazil, 05403-000
    • Local Institution - 0003
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-270
      • Local Institution - 0059
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Local Institution - 0101
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Local Institution - 0049
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Local Institution - 0112
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Local Institution - 0050
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 0017
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500587
      • Local Institution - 0280
    • Santiago, Santiago Metropolitan, Chile, 7500921
      • Local Institution - 0278
    • Santiago, Santiago Metropolitan, Chile, 7580206
      • Local Institution - 0276
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0277
• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Local Institution - 0109
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Local Institution - 0217
    • Beijing, Beijing Municipality, China, 100730
      • Local Institution - 0030
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400016
      • Local Institution - 0223
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Local Institution - 0220
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Local Institution - 0266
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150010
      • Local Institution - 0038
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Local Institution - 0194
  • Hubei
    • Wuhan, Hubei, China, 430058
      • Local Institution - 0108
  • Hunan
    • Changsha, Hunan, China, 410008
      • Local Institution - 0089
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Local Institution - 0032
    • Suzhou, Jiangsu, China, 215006
      • Local Institution - 0083
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Local Institution - 0079
  • Jilin
    • Changchun, Jilin, China, 130021
      • Local Institution - 0043
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Local Institution - 0048
  • Shandong
    • Qingdao, Shandong, China, 266003
      • Local Institution - 0111
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Local Institution - 0218
  • Shanxi
    • Xi’an, Shanxi, China, 710068
      • Local Institution - 0216
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0075
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Local Institution - 0103
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Local Institution - 0029
    • Ningbo, Zhejiang, China, 315010
      • Local Institution - 0281
    • Wenzhou, Zhejiang, China, 32500
      • Local Institution - 0033
• Colombia
  • Montería, Colombia, 230002
    • Local Institution - 0149
  • Antioquia
    • Medellín, Antioquia, Colombia, 05034
      • Local Institution - 0147
  • Cesar Department
    • Valledupar, Cesar Department, Colombia, 200001
      • Local Institution - 0152
  • Santander Department
    • Piedecuesta, Santander Department, Colombia, 681017
      • Local Institution - 0267
• Czechia
  • Prague, Czechia, 12808
    • Local Institution - 0090
  • Brno-město
    • Brno, Brno-město, Czechia, 625 00
      • Local Institution - 0080
  • Moravian-Silesian Region
    • Ostrava, Moravian-Silesian Region, Czechia, 708 52
      • Local Institution - 0092
• France
  • Paris, France, 75010
    • Local Institution - 0015
  • Toulouse, France, 31100
    • Local Institution - 0140
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06202
      • Local Institution - 0011
  • Aquitaine
    • Pessac, Aquitaine, France, 33600
      • Local Institution - 0016
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37032
      • Local Institution - 0019
  • Isère
    • La Tronche, Isère, France, 38700
      • Local Institution - 0116
  • Lorraine
    • Vandœuvre-lès-Nancy, Lorraine, France, 54511
      • Local Institution - 0165
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • Local Institution - 0269
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Local Institution - 0248
• Germany
  • Berlin, Germany, 10117
    • Local Institution - 0169
  • Berlin, Germany, 14195
    • Local Institution - 0028
  • Düsseldorf, Germany, 40225
    • Local Institution - 0207
  • Lübeck, Germany, 23562
    • Local Institution - 0255
  • Mutlangen, Germany, 73557
    • Local Institution - 0167
  • Würzburg, Germany, 97080
    • Local Institution - 0166
  • Bavaria
    • Erding, Bavaria, Germany, 85435
      • Local Institution - 0261
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48153
      • Local Institution - 0259
  • Rhineland-Palatinate
    • Koblenz, Rhineland-Palatinate, Germany, 56068
      • Local Institution - 0168
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Local Institution - 0171
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Local Institution - 0251
• Greece
  • Achaḯa
    • Pátrai, Achaḯa, Greece, 26504
      • Local Institution - 0132
  • Anatolikí Makedonía Kai Thráki
    • Alexandroupoli, Anatolikí Makedonía Kai Thráki, Greece, 681 00
      • Local Institution - 0082
  • Attikí
    • Athens, Attikí, Greece, 115 27
      • Local Institution - 0084
    • Athens, Attikí, Greece, 11527
      • Local Institution - 0245
    • Chaïdári, Attikí, Greece, 12462
      • Local Institution - 0131
• Hungary
  • Budapest, Hungary, 1088
    • Local Institution - 0026
  • Heves County
    • Eger, Heves County, Hungary, 3300
      • Local Institution - 0024
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
      • Local Institution - 0021
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380009
      • Local Institution - 0243
  • Karnataka
    • Bengaluru, Karnataka, India, 560027
      • Local Institution - 0177
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • Local Institution - 0193
    • New Delhi, National Capital Territory of Delhi, India, 110085
      • Local Institution - 0235
  • Odisha
    • Bhubaneswar, Odisha, India, 751003
      • Local Institution - 0178
• Italy
  • Bologna, Italy, 40138
    • Local Institution - 0135
  • Reggio Calabria, Italy, 89133
    • Local Institution - 0076
  • Roma, Italy, 00168
    • Local Institution - 0244
  • Verona, Italy, 37134
    • Local Institution - 0133
  • Lazio
    • Rome, Lazio, Italy, 00133
      • Local Institution - 0256
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Local Institution - 0137
  • Milano
    • Milan, Milano, Italy, 20162
      • Local Institution - 0134
    • Rozzano, Milano, Italy, 20089
      • Local Institution - 0136
  • Piedmont
    • Turin, Piedmont, Italy, 10128
      • Local Institution - 0085
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Local Institution - 0138
• Mexico
  • Mexico City, Mexico, 14080
    • Local Institution - 0142
  • Puebla City, Mexico, 72424
    • Local Institution - 0150
  • Oaxaca
    • Oaxaca City, Oaxaca, Mexico, 68020
      • Local Institution - 0156
  • State of Mexico
    • Huixquilucan, State of Mexico, Mexico, 52787
      • Local Institution - 0069
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution - 0060
  • Katowice, Poland, 40-519
    • Local Institution - 0061
  • Warsaw, Poland, 02-172
    • Local Institution - 0062
  • Lower Silesian Voivodeship
    • Wałbrzych, Lower Silesian Voivodeship, Poland, 58-309
      • Local Institution - 0130
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Local Institution - 0219
• Spain
  • Granada, Spain, 18012
    • Local Institution - 0199
  • Madrid, Spain, 28006
    • Local Institution - 0252
  • Oviedo, Spain, 33011
    • Local Institution - 0271
  • Salamanca, Spain, 37007
    • Local Institution - 0200
  • Seville, Spain, 41013
    • Local Institution - 0274
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Local Institution - 0198
  • Catalunya [Cataluña]
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 08908
      • Local Institution - 0197
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • Local Institution - 0196
• United States
  • California
    • Clovis, California, United States, 93611
      • Local Institution - 0070
    • Fountain Valley, California, United States, 92708
      • Local Institution - 0179
    • Los Alamitos, California, United States, 90720
      • Local Institution - 0211
    • Los Angeles, California, United States, 90095
      • Local Institution - 0258
    • Orange, California, United States, 92868
      • Local Institution - 0247
    • Oxnard, California, United States, 93030
      • Local Institution - 0209
    • Walnut Creek, California, United States, 94598
      • Local Institution - 0183
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Local Institution - 0227
    • New Haven, Connecticut, United States, 06510
      • Local Institution - 0173
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Health Medical Center
    • Fort Myers, Florida, United States, 33901
      • Local Institution - 0202
    • Jacksonville, Florida, United States, 32207
      • Local Institution - 0180
    • Margate, Florida, United States, 33063
      • Local Institution - 0224
    • Plantation, Florida, United States, 33322
      • Local Institution - 0163
    • St. Petersburg, Florida, United States, 33705
      • Local Institution - 0201
    • Tamarac, Florida, United States, 33321
      • Local Institution - 0238
    • Tampa, Florida, United States, 33612
      • Local Institution - 0106
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Local Institution - 0240
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0272
    • Skokie, Illinois, United States, 60077
      • Local Institution - 0184
  • Indiana
    • Dyer, Indiana, United States, 46311
      • Local Institution - 0270
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Local Institution - 0191
    • Covington, Louisiana, United States, 70433
      • Local Institution - 0044
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Local Institution - 0007
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Local Institution - 0222
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Local Institution - 0128
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0212
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0206
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Local Institution - 0174
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 0228
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Local Institution - 0236
    • Roanoke, Virginia, United States, 24014
      • Local Institution - 0229
  • Washington
    • Kennewick, Washington, United States, 99336
      • Local Institution - 0203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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 ≤ 3.5 IPSS-R score) confirmed via bone marrow aspirate and:.

  i) < 5% blasts in bone marrow and < 1% blasts in peripheral blood.

• Participant is not transfusion dependent (NTD) based on IWG2018 criteria.
• Participant is erythropoiesis-stimulating agent naive. Participants may be randomized at the investigator's discretion if the participant received no more than 2 prior doses of epoetin alfa, epoetin alfa biosimilar, or darbepoetin alfa, with the last dose at least 8 weeks prior to randomization.
• Participant has a baseline endogenous serum erythropoietin (sEPO) level of ≤ 500 U/L.

• Participant has symptoms of anemia:.

  i) 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.

• Participant has a baseline Hb concentration prior to randomization of ≤ 9.5 g/dL. The baseline Hb will be calculated using the mean of the two lowest available Hb measurements within 16 weeks prior to randomization and must include at least one central lab Hb reading done within the screening period (no more than 35 days before randomization). The two Hb measurements must have been performed at least seven days apart. Hb levels less than 21 days following RBC transfusion should not be used. Split samples for local assessments are not required.

Exclusion Criteria

• Participant with secondary MDS (that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
• Participant with known history of diagnosis of AML.
• Participant with history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis within 6 months prior to randomization.
• Participant with a history of pure red cell aplasia and/or antibody against erythropoietin.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Luspatercept	Biological: Luspatercept; Specified dose on specified days; Other Names: ACE-536; BMS-986346; Reblozyl®
Active Comparator: Epoetin Alfa	Biological: Epoetin Alfa; Specified dose on specified days; Other Names: PROCRIT®; Epogen®; BINOCRIT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with lower-risk non-transfusion dependent myelodysplastic syndromes (NTD-MDS) who converted to Transfusion Dependence (TD) during any continuous 16-week interval within the 96-week treatment period	TD is defined as ≥ 3 red blood cells (RBC) units/16 weeks assessed by International Working Group (IWG) 2018.	Up to Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 grams/deciliter (g/dL) in any continuous 16-week interval within the 48 week Treatment Period in the absence of transfusion		Up to Week 48
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 48
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		From Week 49 to Week 96
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 96
Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 48
Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		From Week 49 to Week 96
Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 96
Mean Hb change over fixed 24-week periods compared to the baseline Hb		Baseline, Week 24, Week 48, Week 72, Week 96
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 96-week treatment period in the absence of transfusion		Up to Week 96
Number of participants with TD by week 48		Up to Week 48
Time to TD (IWG 2018 defined as ≥ 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study		Up to 5 years
Time from first Luspatercept dose to first RBC transfusion		Up to 5 years
Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 48-week treatment period in absence of transfusion		Up to Week 48
Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 96-week treatment period in absence of transfusion		Up to Week 96
Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 48-week Treatment Period in the absence of transfusion)		Up to Week 48
Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 96-week Treatment Period in the absence of transfusion)		Up to Week 96
Number of participants with RBC transfusion independence over at least a consecutive 24-week period		Up to 5 years
Number of transfusions		Up to 5 years
Number of transfusions visits/units		Up to 5 years
Change from baseline in subscales of self-reported health-related quality-of-life (HRQoL) assessed by the Functional Assessment of Cancer Therapy - Anemia (FACT-An)		Baseline, Up to 5 years
Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L)		Baseline, Up to 5 years
Number of participants with adverse events (AEs)		Up to Week 102
Number of participants with antidrug antibody (ADA) (positive or negative)		Up to Week 102
Pharmacokinetics (PK): Serum concentration		Up to Week 96
PK: Area under the plasma concentration time curve (AUC)		Up to Week 96
Number of participants with a platelet response at Week 24, Week 48 and Week 96	Platelet response is defined as an increase from baseline in number of platelets to ≥ 30 × 10^9/L at Week 24, Week 48 and Week 96.	Up to Week 96
Number of participants with a neutrophil response at Week 24, Week 48 and Week 96	Neutrophil response is defined as an absolute increase from baseline of > 0.5 × 10^9/L neutrophils at Week 24, Week 48 and Week 96.	Up to Week 96
Number of participants with acute myeloid leukemia (AML) progression		Up to 5 years
Time to AML progression		Up to 5 years
Number of participants with high risk myelodysplastic syndromes (MDS) progression		Up to 5 years
Time to high-risk MDS progression		Up to 5 years
Time from date of randomization up to death due to any cause		Up to 5 years

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Estimated): June 25, 2027
• Study Completion (Estimated): March 11, 2030

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Epoetin alfa; Luspatercept; ACE-536; Myelodysplastic Syndrome; Myelodysplastic Syndromes (MDS); Anaemia; BMS-986346; Erythropoietin stimulating agent (ESA)
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Anemia; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Erythropoietin; Epoetin Alfa; luspatercept
• Other Study ID Numbers: CA056-025; 2022-500430-29-00 (Other Identifier: EU CTR Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No