A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve (COMMANDS)

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions

The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Randwick, Australia, 2031
    • Local Institution - 212
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Local Institution - 206
    • Blacktown, New South Wales, Australia, 2148
      • Local Institution - 213
    • Concord, New South Wales, Australia, 2139
      • Local Institution - 200
    • Kogarah, New South Wales, Australia, 2217
      • Local Institution - 215
    • Nowra, New South Wales, Australia, 2541
      • Local Institution - 211
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 210
    • Wollongong, New South Wales, Australia, 2500
      • Local Institution - 207
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Local Institution - 208
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 202
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 204
    • Malvern, Victoria, Australia, 3144
      • Local Institution - 203
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 209
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Local Institution - 205
• Austria
  • Linz, Austria, 4020
    • Local Institution - 442
  • Vienna, Austria, 1090
    • Local Institution - 441
• Belgium
  • Antwerpen, Belgium, 2020
    • Local Institution - 475
  • Brasschaat, Belgium, 2930
    • Local Institution - 471
  • Brussels, Belgium, 1200
    • Local Institution - 474
  • Charleroi, Belgium, 6000
    • Local Institution - 472
  • Kortrijk, Belgium, 8500
    • Local Institution - 473
  • Leuven, Belgium, 3000
    • Local Institution - 470
  • Roeselare, Belgium, 8800
    • Local Institution - 476
• Canada
  • Sherbrooke, Canada, J1H 5N4
    • Local Institution - 152
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 147
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution - 145
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 142
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 140
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 141
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Local Institution - 144
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 148
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Local Institution - 151
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Local Institution - 560
  • Ostrava-Poruba, Czechia, 708 52
    • Local Institution - 564
  • Prague 10, Czechia, 100 34
    • Local Institution - 563
  • Praha, Czechia, 128 20
    • Local Institution - 561
  • Praha 2, Czechia, 128 08
    • Local Institution - 562
• France
  • Angers, France, 49000
    • Local Institution - 317
  • Bayonne, France, 64109
    • Local Institution - 312
  • Caen Cedex 9, France, 14033
    • Local Institution - 311
  • La Tronche, France, 38700
    • Local Institution - 306
  • Le Mans, France, 72037
    • Local Institution - 305
  • Lille, France, 59037
    • Local Institution - 309
  • Limoges Cedex, France, 87042
    • Local Institution - 303
  • Nantes Cedex 01, France, 44093
    • Local Institution - 307
  • Nice Cedex 3, France, 06200
    • Local Institution - 301
  • Paris, France, 75010
    • Local Institution - 302
  • Paris, France, 75014
    • Local Institution - 313
  • Pessac, France, 33604
    • Local Institution - 308
  • Pierre Bénite, France, 69495
    • Local Institution - 315
  • Poitiers, France, 86021
    • Local Institution - 316
  • Strasbourg, France, 67033
    • Local Institution - 314
  • Toulouse, France, 31059
    • Local Institution - 300
  • Tours cedex, France, 37044
    • Local Institution - 310
  • Vandoeuvre les Nancy, France, 54511
    • Local Institution - 304
• Germany
  • Baden-Warttemberg, Germany, 73557
    • Local Institution - 422
  • Berlin, Germany, 14195
    • Local Institution - 424
  • Dresden, Germany, 01307
    • Local Institution - 426
  • Duisburg, Germany, 47166
    • Local Institution - 429
  • Dusseldorf, Germany, 40479
    • Local Institution - 420
  • Hamburg, Germany, 22081
    • Local Institution - 431
  • Keil, Germany, 24105
    • Local Institution - 435
  • Koblenz, Germany, 56068
    • Local Institution - 423
  • Köln, Germany, 50677
    • Local Institution - 428
  • Leipzig, Germany, 04103
    • Local Institution - 430
  • Mannheim, Germany, 68167
    • Local Institution - 436
  • Munchen, Germany, 81675
    • Local Institution - 421
  • Winnenden, Germany, 71364
    • Local Institution - 425
  • Würzburg, Germany, 97070
    • Local Institution - 427
• Greece
  • Alexandroupolis, Greece, 08100
    • Local Institution - 396
  • Athens, Greece, 10676
    • Local Institution - 397
  • Athens, Greece, 115 27
    • Local Institution - 391
  • Athens, Greece, 12464
    • Local Institution - 392
  • Athina, Greece, 115 27
    • Local Institution - 395
  • Patras, Greece, 26500
    • Local Institution - 398
  • Rio Patras, Greece, 26500
    • Local Institution - 393
  • Thessaloniki, Greece, 546 36
    • Local Institution - 399
  • Thessaloniki, Greece, 57010
    • Local Institution - 390
  • Irakleio
    • Heraklion, Irakleio, Greece, 71110
      • Local Institution - 389
• Hungary
  • Budapest, Hungary, 1096
    • Local Institution - 535
  • Debrecen, Hungary, 4032
    • Local Institution - 534
  • Nyiregyhaza, Hungary, 4400
    • Local Institution - 536
• Israel
  • Haifa, Israel, 34362
    • Local Institution - 386
  • Jerusalem, Israel, 91120
    • Local Institution - 384
  • Jerusalem, Israel, 9103102
    • Local Institution - 383
  • Kfar-Saba, Israel, 44281
    • Local Institution - 381
  • Nahariya, Israel, 22100
    • Local Institution - 385
  • Tel Aviv, Israel, 64239
    • Local Institution - 382
  • Zerifin, Israel, 70300
    • Local Institution - 380
• Italy
  • Bologna, Italy, 40138
    • Local Institution - 324
  • Firenze, Italy, 50134
    • Local Institution - 327
  • Meldola, Italy, 47014
    • Local Institution - 330
  • Milano, Italy, 20162
    • Local Institution - 321
  • Padova, Italy, 35128
    • Local Institution - 329
  • Reggio Di Calabria, Italy, 89124
    • Local Institution - 326
  • Roma, Italy, 00133
    • Local Institution - 328
  • Roma, Italy, 00189
    • Local Institution - 332
  • Rome, Italy, 00161
    • Local Institution - 325
  • Rozzano, Italy, 20089
    • Local Institution - 323
  • Udine, Italy, 33100
    • Local Institution - 322
  • TO
    • Orbassano, TO, Italy, 10043
      • Local Institution - 331
• Japan
  • Amagasaki-Shi, Japan, 660-0892
    • Local Institution - 247
  • Fujisawa-Shi, Japan, 251-0052
    • Local Institution - 249
  • Fukuoka, Japan, 810-8563
    • Local Institution - 234
  • Hitachi, Ibaraki, Japan, 317-0077
    • Local Institution - 237
  • Kamogawa, Japan, 296-8602
    • Local Institution - 231
  • Kitakyushu-Shi, Japan, 806-0034
    • Local Institution - 248
  • Nagaoka-Shi, Japan, 940-2108
    • Local Institution - 270
  • Nagoya-shi, Japan, 460-0001
    • Local Institution - 243
  • Ogaki, Japan, 503-8502
    • Local Institution - 241
  • Okayama, Japan, 700-8557
    • Local Institution - 235
  • Osaka, Japan, 545-8586
    • Local Institution - 242
  • Sagamihara, Japan, 252-0375
    • Local Institution - 233
  • Sapporo-shi, Japan, 064-0804
    • Local Institution - 246
  • Sendai, Japan, 980-8574
    • Local Institution - 239
  • Shibuya-ku, Japan, 150-8935
    • Local Institution - 232
  • Shimotsuga-gun, Japan, 321-0293
    • Local Institution - 245
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • Local Institution - 230
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Local Institution - 238
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 8528511
      • Local Institution - 244
  • Osaka
    • Osakasayama, Osaka, Japan, 5898511
      • Local Institution - 236
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Local Institution - 251
  • Daegu, Korea, Republic of, 700-721
    • Local Institution - 257
  • Hwasun-Gun, Korea, Republic of, 58128
    • Local Institution - 250
  • Seongnamsi, Korea, Republic of, 13620
    • Local Institution - 253
  • Seoul, Korea, Republic of, 06591
    • Local Institution - 256
  • Seoul, Korea, Republic of, 3080
    • Local Institution - 255
  • Seoul, Korea, Republic of, 5505
    • Local Institution - 254
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 252
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Local Institution - 540
  • Vilnius, Lithuania, LT-08661
    • Local Institution - 541
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 462
  • Den Haag, Netherlands, 2545 CH
    • Local Institution - 461
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 464
  • Rotterdam, Netherlands, 3015 CE
    • Local Institution - 460
  • Sittard-Geleen, Netherlands, 6162 BG
    • Local Institution - 463
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution - 575
  • Lubin, Poland, 20-081
    • Local Institution - 572
  • Poznan, Poland, 60-569
    • Local Institution - 576
  • Rzwszow, Poland, 35-055
    • Local Institution - 573
  • Slupsk, Poland, 76-200
    • Local Institution - 579
  • Walbrzych, Poland, 58-309
    • Local Institution - 578
  • Wroclaw, Poland, 50-367
    • Local Institution - 577
  • Wroclaw, Poland, 50-556
    • Local Institution - 571
  • Lódzkie
    • Lodz, Lódzkie, Poland, 93-513
      • Local Institution - 570
• Portugal
  • Beja, Portugal, 7801-849
    • Local Institution - 373
  • Braga, Portugal, 4710-243
    • Local Institution - 371
  • Lisboa, Portugal, 1099-023
    • Local Institution - 372
  • Porto, Portugal, 4200-072
    • Local Institution - 370
  • Setubal, Portugal, 2910-446
    • Local Institution - 374
• Russian Federation
  • Kaluga, Russian Federation, 248007
    • Local Institution - 511
  • Kirov, Russian Federation, 610027
    • Local Institution - 505
  • Krasnoyarsk, Russian Federation, 660022
    • Local Institution - 509
  • Moscow, Russian Federation, 111123
    • Local Institution - 504
  • Moscow, Russian Federation, 125284
    • Local Institution - 500
  • Moscow, Russian Federation, 123182
    • Local Institution - 507
  • Moscow, Russian Federation, 129301
    • Local Institution - 503
  • Saratov, Russian Federation, 410012
    • Local Institution - 508
  • St Petersburg, Russian Federation, 197341
    • Local Institution - 506
  • St. Petersburg, Russian Federation, 197022
    • Local Institution - 510
  • Tula, Russian Federation, 300053
    • Local Institution - 502
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 358
  • Barcelona, Spain, 08908
    • Local Institution - 350
  • Granada, Spain, 18014
    • Local Institution - 354
  • Madrid, Spain, 28007
    • Local Institution - 352
  • Madrid, Spain, 28041
    • Local Institution - 355
  • Malaga, Spain, 29010
    • Local Institution - 353
  • Murcia, Spain, 30008
    • Local Institution - 361
  • Ourense, Spain, 32005
    • Local Institution - 356
  • Oviedo, Spain, 33011
    • Local Institution - 363
  • Palma de Mallorca, Spain, 7120
    • Local Institution - 362
  • Salamanca, Spain, 37007
    • Local Institution - 351
  • Seville, Spain, 41013
    • Local Institution - 360
  • Valencia, Spain, 46010
    • Local Institution - 357
  • Valencia, Spain, 46026
    • Local Institution - 359
• Sweden
  • Goteborg, Sweden, SE-413 45
    • Local Institution - 550
  • Lund, Sweden, SE-221 85
    • Local Institution - 552
  • Stockholm, Sweden, SE-141 86
    • Local Institution - 551
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 450
  • Luzern 16, Switzerland, 6000
    • Local Institution - 452
  • Winterthur, Switzerland, 8400
    • Local Institution - 451
• Taiwan
  • Changhua City, Changhua, Taiwan, 500
    • Local Institution - 220
  • Niaosong District Kaohsiung City, Taiwan, 83301
    • Local Institution - 222
  • Taichung, Taiwan, 40705
    • Local Institution - 224
  • Taichung City, Taiwan, 40447
    • Local Institution - 223
  • Taipei, Taiwan, 100225
    • Local Institution - 221
• Turkey
  • Ankara, Turkey, 06100
    • Local Institution - 342
  • Manisa, Turkey, 45030
    • Local Institution - 340
  • Trabzon, Turkey, 61080
    • Local Institution - 343
• Ukraine
  • Cherkassy, Ukraine, 18009
    • Local Institution - 526
  • Dnipro, Ukraine, 49102
    • Local Institution - 525
  • Kyiv, Ukraine, 3115
    • Local Institution - 522
  • Lvov, Ukraine, 79044
    • Local Institution - 520
  • Mykolaiv, Ukraine, 54058
    • Local Institution - 523
  • Ternopil, Ukraine, 46002
    • Local Institution - 521
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Local Institution - 401
  • Bournemouth, United Kingdom, BH7 7DW
    • Local Institution - 403
  • Headington, Oxford, United Kingdom, OX3 7LE
    • Local Institution - 405
  • Lincoln, United Kingdom, LN2 5QY
    • Local Institution - 407
  • London, United Kingdom, SE5 9RS
    • Local Institution - 404
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 400
• United States
  • California
    • Berkeley, California, United States, 94704
      • Local Institution - 107
    • San Diego, California, United States, 92123
      • Local Institution - 115
    • Whittier, California, United States, 90603
      • Local Institution - 101
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 104
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Local Institution - 136
  • Florida
    • Hudson, Florida, United States, 34667
      • Local Institution - 119
    • Saint Petersburg, Florida, United States, 33705
      • Local Institution - 120
    • Tallahassee, Florida, United States, 32308
      • Local Institution - 122
    • Tampa, Florida, United States, 33612
      • Local Institution - 108
    • West Palm Beach, Florida, United States, 33401
      • Local Institution - 118
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Local Institution - 102
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Local Institution - 123
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Local Institution - 117
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Local Institution - 134
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 113
  • North Carolina
    • Greenville, North Carolina, United States, 27858-4354
      • Local Institution - 105
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 131
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Univ of Pittsburgh Medical Center
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Local Institution - 111
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1625
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Local Institution - 109
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Local Institution - 114
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Local Institution - 132
    • Chesapeake, Virginia, United States, 23320
      • Local Institution - 127

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of Myelodysplastic syndromes (MDS) according to WHO 2016 classification that meets revised international prognostic scoring system (IPSS-R) classification of very low, low, or intermediate risk disease, and have < 5% blasts in bone marrow
• Endogenous serum erythropoietin (sEPO) level of < 500 U/L
• Requires Red blood cell (RBC) transfusions, as documented by the criteria: Average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells (pRBCs) confirmed for a minimum of 8 weeks immediately preceding randomization
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

Exclusion Criteria:

• Clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any type of known clinically significant bleeding or sequestration or drug induced anemia
• Known history of diagnosis of Acute myeloid leukemia (AML)
• Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment

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	Drug: Luspatercept; Specified dose on specified days; Other Names: ACE-536
Active Comparator: Epoetin alfa	Drug: Epoetin alfa; Specified dose on specified days; Other Names: EPREX®; ERYPO®; PROCRIT®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL	Percentage of participants who are RBC transfusion-free for any 12-week period associated with a concurrent mean hemoglobin (Hgb) increase ≥ 1.5 g/dL compared to baseline. After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated. 4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being < 14 days after the previous transfusion.	Week 1 through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 Weeks	Red blood cell transfusion independence (RBC-TI) for 24 weeks is defined as the percentage of participants who did not receive RBC transfusions from Week 1 through Week 24.	Week 1 through Week 24
Mean Hemoglobin Change Over 24 Weeks	Mean hemoglobin (Hgb) change over the 24-week period of Week 1 through Week 24 compared to baseline. After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated. 4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being < 14 days after the previous transfusion.	Week 1 through Week 24
Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWG	The percentage of participants meeting the modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of >= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of < 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.	Week 1 through Week 24
Time to Hematologic Improvement - Erythroid Response (HI-E)	Time from first dose to first onset of achieving modified HI-E. The modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of >= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of < 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.	Week 1 through Week 24
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)	Percentage of participants who are RBC transfusion-free over a consecutive 84-day period.	Week 1 through Week 24
Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)	Maximum duration of RBC transfusion independence for participants who achieve RBC-TI ≥ 84 days.	Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)	Time from first dose to first onset of transfusion independence ≥ 84 days.	Week 1 through Week 24
Time to First Red Blood Cell (RBC) Transfusion	Time to first RBC transfusion is defined as time from Week 1 to first RBC transfusion on treatment. Participants who maintain RBC-TI through the end of the Treatment Period or time of analysis will be censored at EOT visit date, subsequent MDS therapy start date, study discontinuation date, analysis cutoff date or death, whichever occurs first. Median is from un-stratified Kaplan-Meier method.	Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of Treatment	RBC transfusion burden on treatment is defined as total number of packed red blood cell (pRBC) units transfused within the first 24 weeks of treatment since Week 1.	Week 1 through Week 24
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)	Defined as percentage of participants achieving RBC-TI for >= 56 days during any consecutive 56-day period from Week 1 through Week 24.	Week 1 through Week 24
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week Period	Defined as percentage of participants achieving RBC-TI for >= 168 days during any consecutive 168-day period from Week 1 through Week 48.	Week 1 through Week 48
The Number of Participants With Acute Myeloid Leukemia (AML) Progression	Progression to AML is defined as a diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.	From randomization to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
Median Time to Acute Myeloid Leukemia (AML) Progression	Time to AML progression is defined as the time between randomization and first diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with diagnosis of AML will be considered to have had an event. Participants who have not progressed to AML at the time of analysis will be censored at the last assessment date which does not indicate progression to AML estimated by Kaplan-Meier method.	From randomization to first diagnosis of AML up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
Overall Survival (OS)	Time from date of randomization to death due to any cause	Randomization to death due to any cause up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
The Number of Participants With Adverse Events (AEs)	Treatment-emergent adverse events include adverse events that started on or after the first dose of treatment until 42 days after the last dose of treatment, as well as those serious adverse events (SAEs) made known to the investigator at any time thereafter that are suspected of being related to treatment. The severity/intensity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0). Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.	From first dose to 42 days post last dose (Up to approximately an average of 72 weeks and a maximum of 208 weeks)
Number of Participants With a Positive Anti-drug Antibody (ADA) Test	Number of participants under each ADA positive category. A participant is counted as 'Treatment-Emergent' if there is a positive post-baseline sample while the baseline sample is ADA negative, or there is a positive post-baseline sample with a titer >= 4-fold of the baseline titer while the baseline sample is ADA positive. A participant is counted as 'Preexisting' if the baseline sample is ADA positive and the participant is not qualified for 'Treatment-Emergent'. If the participant was discontinued from study treatment earlier than one year from the first dose, additional samples will be collected if last ADA is positive. Baseline is defined as the last value on or before the first dose of study drug.	Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)	The EORTC QLQ-C30 is composed of 30 items that includes a global health status score ranging from: 1-7 as well as scores for 5 functional scales (physical, role, emotional, cognitive and social), 3 symptom scales (fatigue, nausea/vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) all ranging from 1-4. Subscale scores are transformed to a 0 to 100 scale. A high score for a functional scale represents a high or healthy level of functioning; a high score for the global health status/health related quality of life (HRQoL) represents a high overall HRQoL; but a high score for a symptom scale represents a high level of symptomatology or problems. Baseline is defined as the last value on or before the first dose of study drug.	Baseline and week 24.
Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An)	The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) (so that 0 is considered worse quality of life and 4 is good response) on five primary subscales: Physical well-being (sum of 7 items, score range from 0-28); Social/Family well-being (sum of 7 items, score range from 0-28); Emotional well-being (sum of 6 items, score range from 0-24); Functional well-being (sum of 7 items, score range from 0-28); Anemia-related symptoms (sum of 20 items, score range from 0-80) A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug.	Baseline, Day 1 on weeks 7,13,19, and 24.
Area Under the Concentration-time Curve [AUC]		Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
Maximum Plasma Concentration of Drug [Cmax]		Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose

Collaborators and Investigators

• Sponsor: Celgene
• Collaborators: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): September 28, 2027

Study Registration Dates

• First Submitted: September 7, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 24, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Erythropoietin; Anemia; Blood Transfusion; Myelodysplastic Syndromes; Luspatercept; ACE-536; Myelodysplasia; RBC Transfusion; Erythropoiesis-stimulating agents; Epoetin alpha
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Anemia; Hematinics; Epoetin Alfa; Luspatercept
• Other Study ID Numbers: ACE-536-MDS-002; U1111-1218-1810 (Registry Identifier: WHO); 2022-501485-22 (Other Identifier: EU CTR)

Drug and device information, study documents

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