A Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With International Prognostic Scoring System Revised (IPSS-R) Low- or Intermediate-risk Myelodysplastic Syndrome (MDS)

A Phase 2/3, Multicenter, Randomized, Dose Optimization (Part I), Double-blind (Part II) Study to Compare the Efficacy and Safety of Oral Azacitidine (Oral-Aza, ONUREG®) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With IPSS-R Low- or Intermediate-risk Myelodysplastic Syndrome (MDS)

The purpose of this study is to evaluate the safety and efficacy of oral azacitidine in participants with low to intermediate International Prognostic Scoring System Revised (IPSS-R) myelodysplastic syndrome (MDS).

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Oral Azacitidine; Drug: Placebo for Oral Azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, CP1280AEB
    • Local Institution - 0050
  • Buenos Aires, Argentina, 1425
    • Local Institution - 0016
  • Buenos Aires, Argentina, 1431
    • Local Institution - 0022
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, 1629
      • Local Institution - 0070
  • Buenos Aires F.D.
    • ABB, Buenos Aires F.D., Argentina, C1199ABB
      • Local Institution - 0039
• Australia
  • Melbourne, Australia, 3004
    • Local Institution - 0003
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0006
    • Melbourne, Victoria, Australia, 3000
      • Local Institution - 0018
    • Melbourne, Victoria, Australia, 3065
      • Local Institution - 0004
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 0008
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0015
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Local Institution - 0090
• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Local Institution - 0156
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 0060
• Denmark
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Local Institution - 0115
  • North Denmark
    • Aalborg, North Denmark, Denmark, 9000
      • Local Institution - 0116
• France
  • Paris, France, 75010
    • Local Institution - 0082
  • Aquitaine
    • Pessac, Aquitaine, France, 33600
      • Local Institution - 0063
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37032
      • Local Institution - 0024
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • Local Institution - 0094
  • Nord
    • Lille, Nord, France, 59000
      • Local Institution - 0056
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Local Institution - 0085
• Germany
  • Dresden, Germany, 01307
    • Local Institution - 0037
  • Hamburg, Germany, 22081
    • Local Institution - 0007
  • Mutlangen, Germany, 73557
    • Local Institution - 0028
  • North Rhine-Westphalia
    • Duisburg, North Rhine-Westphalia, Germany, 47166
      • Local Institution - 0081
    • Düsseldorf, North Rhine-Westphalia, Germany, 40479
      • Local Institution - 0128
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Local Institution - 0055
• Greece
  • Alexandroupoli, Greece, 08100
    • Local Institution - 0127
  • Attikí
    • Chaïdári, Attikí, Greece, 12462
      • Local Institution - 0125
  • Thessaloníki
    • Thessaloniki, Thessaloníki, Greece, 570 10
      • Local Institution - 0129
• Hong Kong
  • Hksar, Hong Kong
    • Local Institution - 0178
  • Shatin, Hong Kong, NT
    • Local Institution - 0180
• Italy
  • Bologna, Italy, 40138
    • Local Institution - 0101
  • Lazio
    • Rome, Lazio, Italy, 00133
      • Local Institution - 0061
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Local Institution - 0052
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Local Institution - 0075
• Japan
  • Osaka, Japan, 545-8586
    • Local Institution - 0124
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan, 8068501
      • Local Institution - 0136
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 064-0804
      • Local Institution - 0154
  • Hyōgo
    • Amagasaki, Hyōgo, Japan, 660-8550
      • Local Institution - 0153
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Local Institution - 0130
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Local Institution - 0135
  • Tokyo
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • Local Institution - 0150
• Poland
  • Warmian-Masurian Voivodeship
    • Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-228
      • Local Institution - 0097
• South Korea
  • Jeonranamdo
    • Hwasun Gun, Jeonranamdo, South Korea, 58128
      • Local Institution - 0058
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 06591
      • Local Institution - 0048
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
      • Local Institution - 0036
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06351
      • Local Institution - 0012
  • Taegu-Kwangyǒkshi
    • Junggu, Taegu-Kwangyǒkshi, South Korea, 41944
      • Local Institution - 0051
• Spain
  • Granada, Spain, 18012
    • Local Institution - 0107
  • Madrid, Spain, 28006
    • Local Institution - 0111
  • Ourense, Spain, 32005
    • Local Institution - 0112
  • Oviedo, Spain, 33011
    • Local Institution - 0110
  • Salamanca, Spain, 37007
    • Local Institution - 0108
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46010
      • Local Institution - 0109
• Sweden
  • Stockholms Län [se-01]
    • Stockholm, Stockholms Län [se-01], Sweden, 141 86
      • Local Institution - 0118
  • Örebro Län [se-18]
    • Örebro, Örebro Län [se-18], Sweden, 701 85
      • Local Institution - 0119
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Local Institution - 0137
    • Tamarac, Florida, United States, 33321
      • Local Institution - 0147
  • New York
    • East Syracuse, New York, United States, 13057
      • Local Institution - 0132
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Local Institution - 0073
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 0086
    • Houston, Texas, United States, 77030
      • Local Institution - 0014
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 0123

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant has a documented diagnosis of MDS according to WHO 2016 classification that meets International Prognostic Scoring System Revised (IPSS-R) classification of low- or intermediate-risk disease (IPSS-R score between 1.5 and 4.5).

MDS diagnosis, WHO classification, and IPSS-R risk classification will be prospectively determined by independent central pathology and cytogenetics review, and applicable central laboratory results.

• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

• Participants with prior malignancies must have an expected median life expectancy of at least 12 months at the time of inclusion and no active treatment of any sort for at least 24 weeks prior to randomization (including but not limited to immunotherapy or targeted therapy)
• Hypoplastic Myelodysplastic Syndrome (MDS) with a marrow cellularity of ≤ 10%
• Participants diagnosed with MDS with excess blasts-2 (MDS-EB2)
• Prior treatment with azacitidine (any formulation), decitabine, or other hypomethylating agent

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: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I - Oral-Aza (Dose 1)	Drug: Oral Azacitidine; Specified dose on specified days; Other Names: BMS-986345; Oral-Aza; ONUREG®
Experimental: Part I - Oral-Aza (Dose 2)	Drug: Oral Azacitidine; Specified dose on specified days; Other Names: BMS-986345; Oral-Aza; ONUREG®
Experimental: Part II - Oral-Aza (RP3D); RP3D: Recommended Phase 3 Dose	Drug: Oral Azacitidine; Specified dose on specified days; Other Names: BMS-986345; Oral-Aza; ONUREG®
Experimental: Part II - Placebo	Drug: Placebo for Oral Azacitidine; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs) evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria v.5.0	Phase 2	6 cycles plus 28 days (up to 24 weeks)
Number of participants who achieved complete remission (CR) per International Working Group (IWG) 2006 criteria within 6 cycles	Phase 2 and 3	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who achieved Overall Response (OR) per IWG 2006 criteria within 6 cycles	Phase 2 and Phase 3 Overall Response is defined as complete response (CR), partial remission (PR), marrow complete response (mCR), hematologic improvement-erythroid response (HI-E), hematologic improvement-platelet response (HI-P), or hematologic improvement-neutrophil response (HI-N) as per IWG 2006 criteria	Up to 24 weeks
Number of participants who achieved 84-day packed red blood cells transfusion independence (pRBC-TI)	Phase 2 and Phase 3	Up to 32 weeks
pRBC-TI duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Number of participants who achieve 84 day platelet transfusion independence (PLT-TI) within 6 cycles	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
PLT-TI duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Number of participants who achieved pRBC transfusion reduction	Phase 3	Over the course of the study, an average of 1 year
pRBC transfusion reduction duration	Phase 3	Over the course of the study, an average of 1 year
CR duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Best OR	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
OR duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Overall Survival (OS)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Event-free Survival (EFS)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Time to acute myeloid leukemia (AML)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Time to subsequent therapy	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Iron parameters measured from blood	Phase 3	Over the course of the study, an average of 1 year
Number of participants with Adverse Events (AEs) evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria v.5.0	Phase 3	Up to end of treatment/early termination, an average of 1 year
Summary statistics for Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Summary statistics for Quality of Life in Myelodysplasia Scale (QUALMS) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Summary statistics for the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Number of participants with healthcare resource use associated with the investigational product (IP)	Phase 3	Over the course of the study, an average of 1 year

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): December 14, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: July 8, 2022
• First Submitted That Met QC Criteria: July 19, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Thrombocytopenia
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Bone Marrow Diseases; Blood Platelet Disorders; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Thrombocytopenia; Anemia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine
• Other Study ID Numbers: CA055-026; U1111-1276-5463 (Other Grant/Funding Number: WHO)

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