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

NCT05664737 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CA056-0152022-502328-35
• Study Type: interventional
• Target: 189
• Locations: 11 countries
• Sites: 36

Brief Summary

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.

Conditions

Anemia

Keywords

Luspatercept; BMS-986346; ACE-536; α-thalassemia; Alpha Thalassemia; Reblozyl; Transfusions; Non-transfusion dependent; RBC transfusion dependent

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (64)

• 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

  Up to Week 108

• The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units

  Up to Week 108

• Number of RBC transfusion units from week 1 to week 48

  Up to Week 48

• Change from baseline in hemoglobin in the absence of transfusion at Week 24

  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

  Up to Week 108

Study Arms (4)

Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC)

EXPERIMENTAL

Biological: Luspatercept

Adult TD Cohort: Placebo + BSC

PLACEBO COMPARATOR

Drug: Placebo

Non-transfusion Dependent (NTD): Luspatercept + BSC

EXPERIMENTAL

Biological: Luspatercept

Adult NTD Cohort: Placebo + BSC

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Specified dose on specified days

Adult NTD Cohort: Placebo + BSC; Adult TD Cohort: Placebo + BSC

Luspatercept BIOLOGICAL

Specified dose on specified days

Also known as: BMS-986346, ACE-536, REBLOZYL

Non-transfusion Dependent (NTD): Luspatercept + BSC; Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participant≥ 18 years with documented diagnosis of A-Thal HbH disease with Transfusion dependence defined as:.
• TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization.
• NTD participant:\< 6 RBC units during the 24 weeks prior to randomization(transfusion due to conditions other than A-Thal will not be considered)and, RBC transfusion-free during at least 8 weeks prior to randomization(unless transfusion was required to treat an acute medical condition other than A-Thal) 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.
• Adult participant has Eastern Cooperative Oncology Group (ECOG) 34 score of 0 or 1.
• Adolescent participant 12 years to \< 18 years with documented diagnosis of A-Thal HbH disease with transfusion dependence defined as:.
• TD participant: ≥ 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.
• NTD participant:\< 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.
• Participant has Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status score ≥ 50 at screening.

You may not qualify if:

• Medical Conditions: Diagnosis of A-ThalTrait, Hb Bart hydrops, ATRx A-Thal, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation. Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias. Undergone episodes of hemolysis not related to A-Thal within the 8 weeks prior to randomization.
• Participant has deep vein thrombosis (DVT), stroke or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24weeks prior to randomization.
• Participant has uncontrolled hypertension. Controlled hypertension for this protocol is considered: blood pressure value corresponding to ≤Grade 1 according to NCI CTCAE Version 5.0. with or without pharmacological treatment.
• Reproductive Status: Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding.
• Prior/Concomitant: Undergone HSCTs or gene therapy (candidates for HSCT or gene therapy with waiting period of ≥ 12 months are eligible).
• Use of hydroxyurea treatment ≤ 12 weeks prior to enrollment for NTD participants and ≤ 24 weeks for TD participants.
• Participant who has extramedullary hematopoiesis (EMH) complications requiring treatment to control the growth of EMH mass(es) during the screening period.
• Any medical or psychiatric condition (including active infections, recent surgery, sequelae of diseases or interventions, clinically significant laboratory abnormalities or concurrent treatment) that in the opinion of the investigator would put the participant at unacceptable risk of participating in the study or that could affect interpretability of data.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (36)

Local Institution - 0008

Halifax, Nova Scotia, B3K 6R8, Canada

WITHDRAWN

Sun Yat-sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, GD, 510120, China

RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, GD, 510515, China

RECRUITING

The First People's Hospital of Foshan

Foshan, Guangdong, 528000, China

RECRUITING

Maoming People's Hospital

Maoming Shi, Guangdong, 525000, China

RECRUITING

Shenzhen Second People's Hospital

Shenzhen Shi, Guangdong, 518025, China

RECRUITING

Liuzhou People's Hospital

Liuchow, Guangxi, 545006, China

RECRUITING

People's Liberation Army The 923rd Hospital

Nanning, GX, 530021, China

RECRUITING

Local Institution - 0011

Haikou, Hainan, 570203, China

ACTIVE NOT RECRUITING

Local Institution - 0012

Kunming, Yunnan, 650032, China

COMPLETED

Hainan General Hospital

Haikou, 570311, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, 530021, China

RECRUITING

Local Institution - 0005

Thessaloniki, B, 546 42, Greece

WITHDRAWN

Local Institution - 0007

Larissa, E, 412 21, Greece

ACTIVE NOT RECRUITING

Local Institution - 0018

Rio, G, 265 04, Greece

ACTIVE NOT RECRUITING

Local Institution - 0006

Athens, 115 27, Greece

ACTIVE NOT RECRUITING

Local Institution - 0009

Goudi, 11527, Greece

ACTIVE NOT RECRUITING

Local Institution - 0025

Hong Kong, HK, Hong Kong

COMPLETED

Local Institution - 0024

Hong Kong Island, Hong Kong

WITHDRAWN

Local Institution - 0022

Cagliari, CA, 09121, Italy

WITHDRAWN

Local Institution - 0026

Genova, GE, 16128, Italy

ACTIVE NOT RECRUITING

Local Institution - 0020

Orbassano, TO, 10043, Italy

ACTIVE NOT RECRUITING

Local Institution - 0028

Naples, 80131, Italy

ACTIVE NOT RECRUITING

"Universita degli Studi della Campania ""Luigi Vanvitelli"" - AOU - Clinica Pediatrica"

Naples, 80138, Italy

RECRUITING

Hospital Tunku Azizah

Kuala Lumpur, WP, 50586, Malaysia

RECRUITING

Hospital Sultanah Aminah

Johor Bahru, 80100, Malaysia

RECRUITING

Local Institution - 0035

Al-Ahsa, 31982, Saudi Arabia

WITHDRAWN

King Saud University (KSU) - College of Medicine

Riyadh, 11411, Saudi Arabia

RECRUITING

KK Women's and Children's Hospital

Singapore, 229899, Singapore

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, KHH, 807, Taiwan

RECRUITING

National Taiwan University Hospital

Nan Gang Qu, TPE, 10002, Taiwan

RECRUITING

China Medical University Hospital

Taichung, TXG, 40447, Taiwan

RECRUITING

Siriraj Hospital

Bangkok Noi, Bangkok, 10700, Thailand

RECRUITING

Naresuan University Hospital

Mueang Phitsanulok, 65000, Thailand

RECRUITING

Hacettepe Üniversitesi Tıp Fakültesi

Altındağ, 06230, Turkey (Türkiye)

RECRUITING

Istanbul Universitesi - Istanbul Tip Fakultesi (ITF) Hastanesi

Topkapı, 34093, Turkey (Türkiye)

RECRUITING

Related Publications (1)

• Diamantidis MD, Pitsava S, Zayed O, Argyrakouli I, Karapiperis K, Chatzoulis C, Alexiou E, Manafas A, Tsangalas E, Karakoussis K. Concomitant Presence of Hb Agrinio and - -Med Deletion in a Greek Male Patient with Hemoglobinopathy H: More Severe Phenotype and Literature Review. Hematol Rep. 2023 Aug 8;15(3):483-490. doi: 10.3390/hematolrep15030050.

  PMID: 37606495 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Anemia; alpha-Thalassemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 27, 2022
• Study Start: December 9, 2022
• Primary Completion (Estimated): July 16, 2027
• Study Completion (Estimated): August 14, 2034
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

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

Locations

CA (1); CN (11); IT (5); HK (2); SG (1); TU (2); TW (3); MY (2); GR (5); TH (2); SA (2)