A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions

A Phase 2, Multicenter, Single-Arm Bridging Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes(MDS) in Chinese and Japanese Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions

The purpose of this study is to evaluate the efficacy and safety of luspatercept (ACE-536) for the treatment of anemia due to Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) in Chinese and Japanese participants with ring sideroblasts who require Red Blood Cells (RBC) transfusions.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Local Institution - 100
  • Chengdu, Sichuan, China, 610041
    • Local Institution - 107
  • Guangzhou, China, 510060
    • Local Institution - 105
  • Guangzhou, China, 510080
    • Local Institution - 103
  • Guangzhou, China, 510515
    • Local Institution - 109
  • Hangzhou City, China, 310006
    • Local Institution - 102
  • Nanchang, China, 330006
    • Local Institution - 112
  • Nanjing, China, 210029
    • Local Institution - 108
  • Shanghai, China
    • Local Institution - 114
  • Shanghai, China, 200233
    • Local Institution - 101
  • Suzhu, China, 215006
    • Local Institution - 104
  • Tianjin, China, 300020
    • Local Institution - 106
  • Wenzhou, China, 325000
    • Local Institution - 111
  • Wuhan, China, 430022
    • Local Institution - 110
• Japan
  • Kamogawa, Japan, 296-8602
    • Local Institution - 206
  • Mibu-Machi, Japan, 321-0293
    • Local Institution - 201
  • Ogaki, Japan, 503-8502
    • Local Institution - 208
  • Osaka, Japan, 545-8585
    • Local Institution - 205
  • Sagamihara, Japan, 252-0375
    • Local Institution - 204
  • Sendai, Japan, 980-8574
    • Local Institution - 207
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • Local Institution - 202
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Local Institution - 209
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8511
      • Local Institution - 203
  • Osaka
    • Osakasayama, Osaka, Japan, 5898511
      • Local Institution - 210

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Refractory or intolerant to, or ineligible for, prior Erythropoiesis stimulating agent (ESA) treatment as defined by any one of the following: Refractory to prior ESA treatment, Intolerant to prior ESA treatment, or ESA ineligible.
• previously treated with an ESA or granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, both agents must have been discontinued ≥ 4 weeks prior to date of luspatercept treatment
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

Exclusion Criteria:

• Prior therapy with disease modifying agents for underlying MDS disease
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Luspatercept Administration	Drug: Luspatercept; Specified dose on specified days; Other Names: ACE-536

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks	Week 1 through Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
RBC-TI ≥ 12 weeks	Week 1 through Week 24
Reduction in Red Blood Cell (RBC) units transfused over 16 weeks compared to baseline	Week 9 through Week 24
Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG)	Week 1 through Week 24
Mean hemoglobin increase ≥ 1.0 g/dL	Week 1 through Week 24
Duration of RBC-TI	Week 1 through Week 24
Mean decrease in serum ferritin compared to baseline	Week 9 through Week 24
Mean decrease in iron chelation therapy (ICT) use compared to baseline	Week 9 through Week 24
Time to RBC-TI	Week 1 through Week 24
Progression to acute myeloid leukemia (AML)	Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
Overall survival (OS)	Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
Incidence of type of adverse events (AEs)	Screening through 42 days post last dose
Incidence of frequency of AEs	Screening through 42 days post last dose
Incidence of severity of AEs	Screening through 42 days post last dose
Incidence of seriousness of AEs	Screening through 42 days post last dose
Incidence of relationship of AEs to study treatment	Screening through 42 days post last dose
Pharmacokinetics - Area under the curve (AUC)	Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
Pharmacokinetics - Maximum plasma concentration of the drug (Cmax)	Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
Frequency of Anti-drug antibodies (ADA)	Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose

Collaborators and Investigators

• Sponsor: Celgene
• 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): November 30, 2020
• Primary Completion (Actual): September 29, 2023
• Study Completion (Estimated): February 23, 2026

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Anemia; MDS; Myelodysplastic Syndromes; Luspatercept; ACE-536
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Anemia; Hematinics; Luspatercept
• Other Study ID Numbers: ACE-536-MDS-004; U1111-1251-9249 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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