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

Sponsor

Celgene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04477850

Collaborator

(none)

Enrollment

Locations

Arm

62.8

Anticipated Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Luspatercept	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 30, 2020

Anticipated Primary Completion Date :

Aug 26, 2023

Anticipated Study Completion Date :

Feb 23, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Luspatercept Administration

Drug: Luspatercept

Specified dose on specified days

Other Names:

ACE-536

Outcome Measures

Primary Outcome Measures

Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks [Week 1 through Week 24]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking Union Medical College Hospital	Beijing		China	100730
2	Local Institution - 107	Chengdu, Sichuan		China	610041
3	West China Hospital	Chengdu, Sichuan		China	610041
4	Sun Yat-sen University Cancer Center	Guangzhou		China	510060
5	Local Institution - 109	Guangzhou		China	510515
6	Nanfang Hospital of Southern Medical University	Guangzhou		China	510515
7	Local Institution - 102	Hangzhou City		China	310006
8	The First Affiliated Hospital of Medical School of Zhejiang University	Hangzhou City		China	310006
9	Local Institution - 113	Hefei		China	230022
10	The First Affiliated Hospital of Anhui Medical University	Hefei		China	230022
11	The First Affiliated Hospital of Nanchang University	Nanchang		China	330006
12	Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University	Nanjing		China	210029
13	Shanghai 6th Hospital	Shanghai		China	200233
14	Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai		China
15	The First Affiliated Hospital of Soochow University	Suzhu		China	215006
16	Institution of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Sciences	Tianjin		China	300020
17	Local Institution - 106	Tianjin		China	300020
18	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou		China	325000
19	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan		China	430022
20	Local Institution - 210	Osakasayama	Osaka	Japan	5898511
21	Kameda Medical Center	Kamogawa		Japan	296-8602
22	Matsuyama Red Cross Hospital	Matsuyama		Japan	790-8524
23	Dokkyo Medical University Hospital	Mibu-Machi		Japan	321-0293
24	Local Institution - 201	Mibu-Machi		Japan	321-0293
25	Local Institution - 203	Nagasaki		Japan	852-8511
26	The Japanese Red Cross Nagasaki Genbaku Hospital	Nagasaki		Japan	852-8511
27	Ogaki Municipal Hospital	Ogaki		Japan	503-8502
28	Kindai University Hospital	Osaka-Sayama		Japan	589-8511
29	Local Institution - 205	Osaka		Japan	545-8585
30	Osaka City University Hospital	Osaka		Japan	545-8585
31	Kitasato University Hospital	Sagamihara		Japan	252-0375
32	Tohoku University Hospital	Sendai		Japan	980-8574
33	Local Institution - 202	Shinagawa-ku, Tokyo		Japan	141-8625
34	NTT Medical Center Tokyo	Shinagawa-ku, Tokyo		Japan	141-8625