A Study to Determine the Efficacy and Safety of Luspatercept in Adult and Adolescent Participants With Alpha (α)-Thalassemia

A Phase 2, Study for the Treatment of Anemia With Alpha (α)-Thalassemia to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) in Adults and Evaluate the Safety and Pharmacokinetics in Adolescents

The purpose of the study is to evaluate the efficacy and safety of luspatercept plus best supportive care (BSC) vs placebo plus BSC on anemia in adult participants with α-thalassemia hemoglobin H (HbH) disease and determine the safety and drug levels in adolescent participants.

Study Overview

• Status: Recruiting
• Conditions: Anemia
• Intervention / Treatment: Drug: Placebo; Biological: Luspatercept

• Study Type: Interventional
• Enrollment (Estimated): 249
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • Withdrawn
      • Local Institution - 0008
• China
  • Haikou, China, 570311
    • Recruiting
    • Hainan General Hospital
    • Contact: Guyun Wang, Site 0002; Phone Number: +8613006021266
  • Haikou, China, 570203
    • Recruiting
    • Local Institution - 0011
    • Contact: Site 0011
  • Liuzhou, China, 545006
    • Recruiting
    • Liuzhou People's Hospital
    • Contact: Qin Liu, Site 0023; Phone Number: 8613978020485
  • Nanning, China, 530021
    • Recruiting
    • The First Affiliated Hospital of Guangxi Medical University
    • Contact: Yongrong Lai, Site 0016; Phone Number: +8613517711828
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Recruiting
      • The First People's Hospital of Foshan
      • Contact: Ying Zhao, Site 0013
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Southern Medical University
      • Contact: Ling Jiang, Site 0015; Phone Number: +8613602791429
    • Maoming Shi, Guangdong, China, 525000
      • Recruiting
      • Maoming People's Hospital
      • Contact: Xiong Zhang, Site 0017; Phone Number: +8606682992967
  • Guangxi
    • Nanning Shi, Guangxi, China, 530021
      • Recruiting
      • People's Liberation Army The 923rd Hospital
      • Contact: Xiaolin Yin, Site 0014; Phone Number: +8613321717899
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Recruiting
      • First People's Hospital of Yunnan Province
      • Contact: Yanmei Yang, Site 0012
• Greece
  • Athens, Greece, 115 27
    • Recruiting
    • "General Hospital ""IPPOKRATEIO"""
    • Contact: Sophia Delicou, Site 0006; Phone Number: 302132088162
  • Goudi, Greece, 11527
    • Recruiting
    • Local Institution - 0009
    • Contact: Site 0009
  • B
    • Thessaloniki, B, Greece, 546 42
      • Recruiting
      • Local Institution - 0005
      • Contact: Site 0005
  • E
    • Larissa, E, Greece, 412 21
      • Recruiting
      • General Hospital of Larissa
      • Contact: Michael Diamantidis, Site 0007
  • G
    • Rio, G, Greece, 265 04
      • Recruiting
      • Local Institution - 0018
      • Contact: Site 0018
• Hong Kong
  • Hong Kong Island, Hong Kong
    • Not yet recruiting
    • Local Institution - 0024
    • Contact: Site 0024
  • HK
    • Hong Kong, HK, Hong Kong
      • Not yet recruiting
      • Local Institution - 0025
      • Contact: Site 0025
• Italy
  • Napoli, Italy, 80138
    • Recruiting
    • Local Institution - 0019
    • Contact: Site 0019
  • Napoli, Italy, 80131
    • Recruiting
    • Local Institution - 0028
    • Contact: Site 0028
  • CA
    • Cagliari, CA, Italy, 09121
      • Active, not recruiting
      • Local Institution - 0022
  • GE
    • Genova, GE, Italy, 16128
      • Recruiting
      • Local Institution - 0026
      • Contact: Site 0026
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • Azienda Ospedaliero - Universitaria San Luigi Gonzaga
      • Contact: Giovanni Battista Ferrero, Site 0020
• Taiwan
  • KHH
    • Kaohsiung, KHH, Taiwan, 807
      • Recruiting
      • Local Institution - 0010
      • Contact: Site 0010
  • TPE
    • Nan Gang Qu, TPE, Taiwan, 10002
      • Recruiting
      • Local Institution - 0004
      • Contact: Site 0004
  • TXG
    • Taichung, TXG, Taiwan, 40447
      • Recruiting
      • China Medical University Hospital
      • Contact: Ching-Tien Peng, Site 0003; Phone Number: 886422052121ext4636
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital
    • Contact: Vip Viprakasit, Site 0001; Phone Number: 6624122113
• Turkey
  • Altındağ, Turkey, 06230
    • Not yet recruiting
    • Local Institution - 0027
    • Contact: Site 0027
  • Topkapı, Turkey, 34093
    • Not yet recruiting
    • Local Institution - 0021
    • Contact: Site 0021

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for TD participants defined as ≥ 6 RBC units during the 24 weeks prior to randomization and no transfusion-free period for > 56 days during the 24 weeks prior to randomization.
• Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 6 RBC units during the 24 weeks prior to randomization and, RBC transfusion-free during at least 8 weeks prior to randomization and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to randomization; hemoglobin values within 21 days post-transfusion will be excluded.
• Adolescent participant 12 years to < 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for TD participants defined as ≥ 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years.
• Adolescent participant 12 years to < 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence for NTD participants defined as < 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded.
• Adolescent participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.

Key Exclusion Criteria:

• Participants must not have a diagnosis of α-thalassemia Trait, Hb Bart hydrops, ATRx α-thalassemia, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation.
• Participants must not have anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias.
• Participants must not have bleeding disorders manifested by frequent bleeding episodes.
• Participants must not have undergone episodes of hemolysis not related to alpha-thalassemia within the 8 weeks prior to randomization.
• Participants must not have prior exposure to gene therapy to treat α-thalassemia.
• Participants must not have undergone hematopoietic stem cell transplantation (HSCT)

Note: 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: Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC)	Biological: Luspatercept; Specified dose on specified days; Other Names: ACE-536; BMS-986346; REBLOZYL
Experimental: Non-transfusion Dependent (NTD): Luspatercept + BSC	Biological: Luspatercept; Specified dose on specified days; Other Names: ACE-536; BMS-986346; REBLOZYL
Placebo Comparator: Adult TD Cohort: Placebo + BSC	Drug: Placebo; Specified dose on specified days
Placebo Comparator: Adult NTD Cohort: Placebo + BSC	Drug: Placebo; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Week 13-48 compared to 12-week interval immediately prior to date of first dose	Adult TD Cohort	Up to Week 48
Number of participants with an increase from baseline of ≥ 1.0 grams (g)/decilitre (dL) in mean hemoglobin (Hb) values over the continuous 12-week interval from Week 13 to Week 24 in the absence of RBC transfusion	Adult NTD Cohort	Up to Week 24
Dose-limiting toxicities (DLTs) defined as observance of ≥ Grade 3-related hemolytic crises or ≥ Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy	Adolescent TD and NTD Cohorts	Up to Week 3
Number of participants with adverse events (AEs)	Adolescent TD and NTD Cohorts	Up to 8.5 years
Pharmacokinetics (PK): Serum concentration of Luspatercept	Adolescent TD and NTD Cohorts	Up to Week 102

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 24-week interval on treatment compared to 24-week interval immediately prior to date of first dose	Adult TD Cohort	Up to Week 108
The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units	Adult TD Cohort	Up to Week 108
Number of RBC transfusion units from week 1 to week 48	Adult and Adolescent TD Cohorts	Up to Week 48
Change from baseline in hemoglobin in the absence of transfusion at Week 24	Adult and Adolescent NTD Cohorts	Up to Week 24
The longest duration of an increase from baseline of ≥ 1.0 g/dL in mean hemoglobin values starting from Week 13 in the absence of transfusion	Adult NTD Cohort	Up to Week 108
Time Duration with an increase from baseline of ≥ 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks	Adult NTD Cohort	Up to Week 48
Number of participants with an increase from baseline of ≥1.0 g/dL in mean Hb values over the continuous 12- week interval in the absence of transfusion	Adult NTD Cohort	Up to Week 24
≥ 3 Increase from Baseline in Functional Assessment of Cancer Therapy Anemia Fatigue Subscale (FACT-An FS) Score from Baseline to the period from Week 13 to Week 24	Adult NTD Cohort	Up to Week 24
Number of participants with AEs	Adult and Adolescent TD and NTD Cohorts	Up to 5 years
Number of participants with laboratory abnormalities	Adult TD and NTD Cohorts	Up to 5 Years
Number of participants with immunogenicity	Adult TD and NTD Cohorts	Up to 5 Years
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden during any continuous 24-week interval within 48 weeks compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden during any continuous 12-week interval compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 108
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose	Adult TD Cohort	Up to Week 48
Change from baseline in total RBC units transfused from Week 1 to Week 24, Week 25 to Week 48, and Week 1 to Week 48	Adult TD Cohort	Up to Week 48
The longest duration of RBC transfusion-free period for participants who achieve transfusion-free period of ≥ 12 weeks	Adult TD Cohort	Up to Week 108
The longest duration of reduction in transfusion burden for participants who achieve a response (rolling 12-week and 24-week response, both for ≥ 33% and ≥ 50% reduction)	Adult TD Cohort	Up to Week 108
Time from first dose to first day of response (rolling 12-week and 24-week response, both for ≥ 33% and ≥ 50% reduction)	Adult TD Cohort	Up to Week 108
Change from baseline in number of transfusion events at Week 48	Adult TD Cohort	Up to Week 48
Number of participants who achieve RBC transfusion-free period of any continuous ≥ 12 weeks during treatment	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Number of participants who achieve RBC transfusion-free period of any continuous ≥ 24 weeks during treatment	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Time to first transfusion	Adult and Adolescent NTD Cohorts	Up to Week 108
Number of transfusions	Adult NTD Cohort	Up to Week 48
Number of transfusion visits/units	Adult NTD Cohort	Up to Week 48
Change from baseline in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 and Week 37 to Week 48 in the absence of transfusions	Adult TD and NTD Cohorts	Up to Week 48
Number of participants achieving an increase from baseline of ≥1.0g/dL or ≥1.5g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24, Week 37 to Week 48 and during any continuous 12-week window within 24 weeks and 48 weeks	Adult NTD Cohort	Up to Week 48
Time from first to last Hb measurement with increase from baseline by ≥ 1.0 g/dL	Adult NTD Cohorts	Up to Week 108
Time to the first increase from baseline of ≥ 1.0 g/dL in mean Hb value	Adolescent NTD Cohort	Up to Week 48
Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week and 24-week interval within 48 weeks in the absence of transfusions	Adult NTD Cohort	Up to Week 48
Change from baseline in self-reported health-related quality of life (HRQoL) assessed by physical component summary (PCS) and mental component summary (MCS) of 36-item short-form health survey version2 (SF-36v2) at Week 24 and Week 48	Adult TD and NTD Cohorts	Up to Week 48
Change from baseline in non-transfusion dependent β-thalassemia patient-reported outcome (NTDT-PRO) Tiredness/weakness (T/W) and shortness of breath (SoB) domain scores from Week 13 to Week 24 and from Week 37 to Week 48	Adult NTD Cohort	Up to Week 48
Change from baseline in FACT-An FS Score at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Change from baseline in Functional Assessment of Cancer Therapy Anemia Anemia Subscale (FACT-An AS) at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Number of participants with at least one hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Rate of hemolytic crises	Adult TD and NTD Cohorts	Up to Week 108
Time to first hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Time to second hemolytic crisis	Adult TD and NTD Cohorts	Up to Week 108
Change from baseline in hemolysis markers at Week 24 and Week 48	Adult TD and NTD Cohorts:	Up to Week 48
Change from baseline in the 6-minute walk test (6MWT) distance at Week 24 and Week 48	Adult NTD Cohort	Up to Week 48
Pharmacokinetics (PK): Serum concentration of Luspatercept	Adult and Adolescent TD and NTD Cohorts	Up to Week 108
Percent Change from Baseline in Biomarkers for Erythropoiesis at Week 84	Adult TD and NTD Cohorts The biomarkers for erythropoiesis to be evaluated include Hb variants including hemoglobin H (HbH), sTfR1, erythropoietin (EPO), growth differentiation factor (GDF11), GDF8, GDF15. The change will be measured as a percentage of change from baseline for all the biomarkers.	Baseline, Week 84
Percent Change from Baseline in Biomarkers and Parameters for Iron Homeostasis at Week 84	Adult TD and NTD Cohorts The biomarkers and parameters for iron homeostasis to be evaluated include hepcidin, erythroferrone (ERFE), serum ferritin, liver iron concentration (LIC), myocardial iron, iron chelation therapy (ICT). The change will be measured as a percentage of change from baseline for all the biomarkers.	Baseline, Week 84
Change in mean corpuscular volume (MCV) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Change in mean corpuscular hemoglobin (MCH) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Change in nucleated red blood cells (nRBC) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
Change in red blood cells (RBC) at Week 48	Adult TD and NTD Cohorts	Baseline, Week 48
The longest duration with reduction from baseline in the RBC transfusion burden	Adolescent TD Cohort	Up to Week 48
The number of participants with ≥ 50% reduction from baseline in RBC transfusion burden during an continuous 12 weeks during Weeks 13-48	Adolescent TD Cohort	Up to Week 48
The number of participants with ≥ 33% reduction from baseline in RBC transfusion burden during an continuous 24 weeks	Adolescent TD Cohort	Up to Week 48
Number of participants achieving an increase from baseline of ≥1.0g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24	Adolescent NTD Cohort	Up to Week 24
Cumulative time (in weeks) with an increase from baseline of ≥1.0g/dL in mean Hb values in absence of RBC transfusions within 48 weeks	Adolescent NTD Cohort	Up to Week 48
Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week interval during week 13 to week 48 in the absence of transfusions	Adolescent NTD Cohort	Up to Week 48
The longest duration with an increase from baseline of ≥1.0g/dL in mean Hb values in absence of transfusions	Adolescent NTD Cohort	Up to Week 48
Number of participants with antidrug antibody (ADA)	Adolescent TD and NTD Cohorts	Up to Week 48
Mean change in biomarkers for hemolysis	Adolescent TD and NTD Cohorts Biomarkers for hemolysis to be evaluated include total/direct/indirect bilirubin, serum lactate dehydrogenase (sLDH), haptoglobin, reticulocytes and nucleated red blood cells, reticulocyte production index (RPI), and urinary urobilinogen	Up to Week 48
Mean change in biomarkers and parameters for iron homeostasis	Adolescent TD and NTD Cohorts The biomarkers and parameters for iron homeostasis to be evaluated include serum ferritin, LIC, myocardial iron concentration (MIC), ICT, myocardial T2(TD participants), and extramedullary hematopoiesis (EMH) mass(es) when present (NTD participants)	Up to 1 Year
Hematologic assessments	Adolescent TD and NTD Cohorts The hematologic assessments to be evaluated are red blood cell count, hemoglobin, hematocrit, reticulocyte count, nucleated red blood cell count, platelet count, mean cell volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, red blood cell morphology, and globin precipitates	Up to Week 48
The change from baseline in the number of health care resource utilization (HCRU)	Adolescent TD and NTD Cohorts	Up to Week 48
Mean change from baseline in Pediatric Quality of Life Inventory (PedsQL) domain scores	Adolescent TD and NTD Cohorts	Up to Week 48
Mean change from baseline EQ-5D-5L utility index	Adolescent TD and NTD Cohorts	Up to Week 48
Mean change from baseline visual analogue scale (VAS) scores	Adolescent TD and NTD Cohorts	Up to Week 48

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 9, 2022
• Primary Completion (Estimated): November 5, 2025
• Study Completion (Estimated): June 18, 2026

Study Registration Dates

• First Submitted: December 9, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Luspatercept; ACE-536; Reblozyl; Transfusions; BMS-986346; α-thalassemia; Alpha Thalassemia; Non-transfusion dependent; RBC transfusion dependent
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Thalassemia; Hematinics; Luspatercept
• Other Study ID Numbers: CA056-015; 2022-502328-35 (EudraCT Number)

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 Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.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