An Efficacy and Safety Study of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in Japanese Subjects Who Are Not Requiring Red Blood Cell Transfusion

NCT03900715 | Completed Phase 2 Results

• 2 other identifiers: ACE-536-MDS-003U1111-1224-6268
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 19

Brief Summary

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This is a Phase 2, multicenter, single-arm study to evaluate the efficacy, safety and Pharmacokinetics (PK) of luspatercept (ACE-536) for the treatment of anemia due to International prognostic scoring system-Revised (IPSS-R) very low, low or intermediate risk Myelodysplastic syndromes (MDS)in Japanese subjects who are not requiring Red blood cell (RBC) transfusion. The study is divided into the Screening Period, a Treatment Period and a Post-Treatment Follow up Period.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic Syndromes; MDS; ACE-536; Anemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Hematologic Improvement in Erythroid Response (HI-E) Per International Working Group (IWG) Through Week 24

  Hematologic improvement is defined as the percent of participants meeting HI-E criteria of \>= 1.5 g/dL increase in hemoglobin (Hgb) sustained over any consecutive 56-day period in the absence of red blood cell (RBC) transfusions from Week 1 Day 1 through Week 24. Participants who discontinued from the Treatment Period without achieving HI-E are counted as non-responders.

  Week 1 Day 1 through Week 24

Secondary Outcomes (15)

• Percentage of Participants Who Achieved Modified Hematologic Improvement in Erythroid Response (mHI-E) Per International Working Group (IWG)

  Week 1 Day 1 through Week 24 and Week 48

• Percentage of Participants Who Achieved Hematologic Improvement in Erythroid Response (HI-E) Per International Working Group (IWG) Through Week 48

  Week 1 Day 1 through Week 48

• Time to Hematologic Improvement in Erythroid Response (HI-E)

  Week 1 Day 1 through Week 24 and Week 48

• Time to Modified Hematologic Improvement in Erythroid Response (mHI-E)

  Week 1 Day 1 through Week 24 and Week 48

• Duration of Hematologic Improvement in Erythroid Response (HI-E)

  Week 1 Day 1 through end of treatment period (up to an average of 74 weeks and maximum of 178 weeks)

Study Arms (1)

Luspatercept Administration

EXPERIMENTAL

Luspatercept will be administered as a subcutaneous injection every 3 week (21 days; Q3W), at an initial dose level of 1.0 mg/kg. Doses may be titrated up starting at dosing visit Week 7 Day 1 (W7D1)

Drug: Luspatercept

Interventions

Luspatercept DRUG

Luspatercept

Luspatercept Administration

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 20 years of age the time of signing the informed consent form (ICF)
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject has a documented diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease, and:
• \< 5% blasts in bone marrow
• Subject has symptomatic anemia with mean Hgb concentration \< 10.0 g/dL from 2 measurements (one performed within 1 day prior to W1D1 and the other performed 7 to 35 days prior to W1D1) that does not require RBC transfusion. If more than one measurement exists in the period of 7 to 35 days prior to W1D1, the most recent value will be used.
• Subject must be TI, as documented by the following criteria:
• No RBC transfusion administered within 16 weeks prior to W1D1 (except transfusions due to blood loss or infection that occurred between 16 and 8 weeks prior to W1D1)
• Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
• Females of childbearing potential (FCBP), defined as a sexually mature woman who:
• \) has achieved menarche at some point, 2) not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must:
• Have two negative pregnancy tests as verified by the investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of W1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence1 from heterosexual contact.
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
• If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding after treatment discontinuation.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject with the any of the following prior treatments for underlying disease:
• Disease modifying agents (eg, immune-modulatory drug \[IMiDs such as lenalidomide\])
• \- Except if the subject received ≤ 1 week of treatment with a disease modifying agent ≥ 8 weeks from W1D1, at the investigator's discretion.
• Hypomethylating agents
• \- Subjects may be enrolled at the investigator's discretion contingent that the subject received no more than 2 injections of HMA. The last dose must be ≥ 8 weeks from the date of W1D1.
• Luspatercept (ACE-536) or sotatercept (ACE-011)
• Allogeneic and/or autologous hematopoietic cell transplant
• Subject with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) according to WHO 2016 classification (ie, chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), BCR-ABL12, juvenile myelomonocytic leukemia (JMML), MDS/MPN unclassifiable.
• Subject with secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
• Subject with known 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. Subject with drug induced anemia (eg, mycophenolate).
• Iron deficiency to be determined by serum ferritin \< 100 μg/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity ≤ 20%\] or bone marrow aspirate stain for iron).
• Subject with known history of diagnosis of AML
• Subject receiving any of the following treatment within 8 weeks prior to W1D1:
• Anticancer cytotoxic chemotherapeutic agent or treatment

Sponsors & Collaborators

• Celgene: lead

Study Sites (19)

Local Institution - 338

Matsuyama, Ehime, 790-8524, Japan

Location

Local Institution - 344

Nagasaki, Nagasaki, 852-8511, Japan

Location

Local Institution - 336

Sayama, Osaka, 5898511, Japan

Location

Local Institution - 345

Chiba, 260-0852, Japan

Location

Local Institution - 334

Fukuoka, 810-8563, Japan

Location

Local Institution - 347

Himeji, 670-8540, Japan

Location

Local Institution - 337

Hitachi, Ibaraki, 317-0077, Japan

Location

Local Institution - 346

Kamakura, 247-8533, Japan

Location

Local Institution - 331

Kamogawa, 296-8602, Japan

Location

Local Institution - 348

Kitakyushu, 806-8501, Japan

Location

Local Institution - 349

Kofu, 400-0027, Japan

Location

Local Institution - 343

Nagoya, 460-0001, Japan

Location

Local Institution - 335

Okayama, 700-8557, Japan

Location

Local Institution - 342

Osaka, 545-8586, Japan

Location

Local Institution - 341

Ōgaki, 503-8502, Japan

Location

Local Institution - 333

Sagamihara, 252-0375, Japan

Location

Local Institution - 339

Sendai, 980-8574, Japan

Location

Local Institution - 332

Shibuya-ku, 150-8935, Japan

Location

Local Institution - 330

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: April 3, 2019
• Study Start: May 20, 2019
• Primary Completion: July 1, 2022
• Study Completion: March 1, 2023
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

JP (19)