Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia

NCT04143724 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: ACE-536-B-THAL-004U1111-1241-41682022-502499-22
• Study Type: interventional
• Target: 99
• Locations: 9 countries
• Sites: 26

Brief Summary

This is a Phase 2a study to evaluate the safety and pharmacokinetics (PK) of luspatercept in pediatric participants with β-thalassemia. The study will be conducted in 2 parts for both transfusion-dependent (TD) and non-transfusion-dependent (NTD) β-thalassemia participants: TD Part A will be in adolescent participants aged 12 to \<18 years with two dose escalation cohorts, followed by a dose expansion cohorts. NTD Part A will be conducted in the same age group participants as TD Part A with dose confirmation and expansion cohorts. After Part A TD participants have completed at least one year of treatment, all available safety data from Part A adolescent participants will be evaluated before initiating TD and NTD Part B in the age group from 6 to \<12 years old. Part B will consist of two dose escalation cohorts for TD and two dose escalation cohorts for NTD. Upon completion of the Treatment Period, participants of any cohort who are benefiting from the study treatment, will be offered the opportunity to continue luspatercept treatment in the Long-term Treatment Period for up to 5 years from their first dose. Participants who discontinue study treatment at any time will continue in the Posttreatment Follow-up Period for at least 5 years from their first dose of luspatercept, or 3 years from their last dose, whichever occurs later, or until they withdraw consent/assent, are lost to follow-up, or the End of Trial, whichever occurs first.

Conditions

Beta-Thalassemia

Keywords

ACE-536; Luspatercept; Pharmacokinetics; Beta-Thalassemia; Red Blood Cell Transfusion

Outcome Measures

Primary Outcomes (6)

• Determination of the Recommended Dose (RD

  Determine the recommended dose of luspatercept that is safe and tolerable in pediatric participants with transfusion-dependent B-thalassemia or non-transfusion-dependent β-thalassemia

  Cycle 1 up to the day before Cycle 2 Day 1 or Study Day 22 if not receiving the second treatment cycle

• Pharmacokinetics - Cmax

  Maximum serum concentration of drug

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

• Pharmacokinetics - AUC

  Area under the curve

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

• Pharmacokinetics (PK) - t1/2

  Half-life

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

• Pharmacokinetics (PK) - CL/F

  Apparent oral clearance

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

• Pharmacokinetics (PK) - Vd/F

  Apparent volume of distribution

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

Secondary Outcomes (6)

• Mean change in Red Blood Cell (RBC) Transfusion Burden for transfusion-dependent β-thalassemia participants

  12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years

• Mean change in hemoglobin levels for non-transfusion-dependent β-thalassemia participants

  12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years

• Immunogenicity

  Time from Cycle 1 Day 1 of Treatment Period up to a maximum of 1 year

• Mean change from baseline in mean daily dose of iron chelation therapy (ICT)

  12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years

• Mean change from baseline in serum ferritin

  12 weeks prior to enrollment; Treatment Period and up to End of Treatment including Long-term Treatment Period - Up to 5 years

Study Arms (9)

Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 years

EXPERIMENTAL

Drug: ACE-536

Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg

EXPERIMENTAL

Drug: ACE-536

Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kg

EXPERIMENTAL

Drug: ACE-536

Interventions

ACE-536 DRUG

Specified dose on specified days

Also known as: Luspatercept, BMS-986346

Cohort 1: TD Dose Escalation Cohort: 12 to < 18 years Luspatercept 0.75 mg/kg; Cohort 2: TD Dose Escalation Cohort: 12 to < 18 years: Luspatercept 1.0 mg/kg; Cohort 3: TD Dose Expansion Cohort: 12 to <18 years Luspatercept 1.0 mg/kg; Cohort 4: TD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg; Cohort 5: TD Dose Escalation Cohort: 6 to <12 years Luspatercept 1.2 mg/kg; Cohort 6: NTD Dose Confirmation Cohort: 12 to < 18 years Luspatercept 1.0 mg/kg; Cohort 7: NTD Dose Expansion Cohort: NTD 12 to < 18 years; Cohort 8: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.0 mg/kg; Cohort 9: NTD Dose Escalation Cohort: 6 to < 12 years Luspatercept 1.2 mg/kg

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants must be 6 years to \< 18 years of age at the time of signing the informed consent form (ICF)/informed assent form (IAF).
• Participants (and when applicable, parent/legal representative) must understand and voluntarily sign an ICF/IAF prior to conducting any study-related assessments/procedures.
• Participants (and when applicable, parent/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
• Participants must have documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia.
• Transfusion dependence (TD):
• a. TD participant i. Participant is regularly transfused, defined as: ≥ 4 RBC transfusion events in the 24 weeks prior to enrollment with no transfusion-free period ≥ 42 days during that period.
• Note: For the purpose of the study, transfusions administered over 2 or 3 consecutive days are considered as part of a single transfusion event. Participant must have a history of regular transfusions for at least 2 years.
• b. NTD participant (ex-US sites only) i. Participant must have received \< 4 RBC transfusion events in the 24 weeks prior to enrollment.
• ii. Participant must not be on a regular transfusion program and must be RBC transfusion-free for at least 8 weeks prior to enrollment.
• iii. Participant must have mean baseline hemoglobin ≤ 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.
• Participants have Karnofsky (age ≥16 years) or Lansky (age \< 16 years) performance status score ≥ 50 at screening.
• Female children of childbearing potential (FCCBP), individuals of childbearing potential (IOCBP), and male (as assigned at birth) participants that have reached puberty (and when applicable, parent/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.
• Female children of childbearing potential, defined as females who have achieved menarche and/or breast development in Tanner Stage 2 or greater and have not undergone a hysterectomy or bilateral oophorectomy and individuals of childbearing potential (IOCBP) defined as a sexually mature woman who has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) must meet the following conditions below (Note: Secondary amenorrhea from any cause does not rule out childbearing potential):
• Medically supervised serum pregnancy tests with a sensitivity of at least 25 mIU/mL must be conducted in Female children of childbearing potential (FCCBP)/ individuals of childbearing potential (IOCBP), including those who commit to complete abstinence. Female children of childbearing potential/ individuals of childbearing potential (IOCBP) must have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy (one of these tests should be performed by central laboratory). Female children of childbearing potential/ individuals of childbearing potential (IOCBP) must agree to ongoing pregnancy testing during the course of the study at the End of Treatment (EOT) visit and at the 9-week Safety Follow-up visit.
• Female participants must, as appropriate to age and at the discretion of the site Investigator, either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective\*\* contraception without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal t1/2 of luspatercept based on multiple-dose PK data) after discontinuation of study therapy.

You may not qualify if:

• Participant has a diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H); β-thalassemia combined with α-thalassemia is allowed.
• Participant has of active hepatitis C (HCV) infection, as demonstrated by a positive HCF-ribonucleic acid (RNS) test of sufficient sensitivity, or active infectious hepatitis B (as demonstrated by the presence of hepatitis B surface antigen (HBsAG) and/or hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) positive, or known positive human immunodeficiency virus (HIV).
• Note: Participants receiving antiviral therapies should have 2 negative HCV-RNA tests 3 months apart before ICF/IAF signature, ie, one test at the end of the antiviral therapy and the second test 3 months following the first test.
• Participant has deep vein thrombosis (DVT), stroke, or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24 weeks prior to enrollment.
• Participant has platelet count \> 1000 x 109/L.
• Participant has treatment with another investigational drug or device ≤ 28 days prior to enrollment.
• Participant has prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
• Participant underwent or is scheduled for HSCT or gene therapy.
• Participant use of iron chelation therapy (ICT), if initiated ≤ 8 weeks prior to enrollment (allowed if initiated \> 8 weeks before or during treatment).
• Participant received treatment with hydroxyurea immunomodulatory drugs IMiDs (such as thalidomide), other fetal Hb (HbF) inducers or erythropoiesis-stimulating agents (ESAs) ≤ 12 weeks prior to enrollment for NTD participants and ≤ 24 weeks for TD participants.
• Participant is pregnant or breastfeeding female or plan to get pregnant during the study.
• 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.
• Participant has major organ damage, including:
• Symptomatic splenomegaly
• Liver disease with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \> 3X the upper limit of normal (ULN) for age

Sponsors & Collaborators

• Celgene: lead
• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: collaborator

Study Sites (26)

Local Institution - 601

Los Angeles, California, 90027, United States

COMPLETED

New York Presbyterian Hospital

New York, New York, 10065-4870, United States

RECRUITING

Southern Medical University Nanfang Hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518028, China

RECRUITING

People's Liberation Army The 923rd Hospital

Nanning, GX, 530021, China

RECRUITING

West China Hospital - Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

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

Guangzhou, 510120, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, 530021, China

RECRUITING

Universitätsklinikum Essen

Essen, 45147, Germany

RECRUITING

Universitatsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

General Children's Hospital "Agia Sophia"

Athens, 115 27, Greece

RECRUITING

Kamala Hospital and Research Center

Hyderabad, Andhra Pradesh, 500052, India

RECRUITING

MCGM - Comprehensive Thalassemia Care, Pediatric Hematology-Oncology & BMT Centre, Borivali (E)

Mumbai, Maharashtra, 400022, India

RECRUITING

Kingsway Hospitals

Nagpur, Maharashtra, 440001, India

RECRUITING

Post Graduate Institute of Child Health

Noida, Uttar Pradesh, 201303, India

RECRUITING

Local Institution - 803

Kolkata, 700094, India

WITHDRAWN

Christian Medical College & Hospital

Vellore, 632004, India

RECRUITING

Ospedale Pediatrico Bambino Gesù IRCCS

Rome, Roma, 00165, Italy

RECRUITING

Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite

Genoa, 16128, Italy

RECRUITING

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Naples, 80131, Italy

RECRUITING

Azienda Ospedaliero Universitaria S. Luigi Gonzaga

Orbassano, 10043, Italy

RECRUITING

Local Institution - 700

Beirut, 0, Lebanon

WITHDRAWN

Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

RECRUITING

Siriraj Hospital Mahidol University

Bangkok, 10700, Thailand

RECRUITING

Ramathibodi Hospital, Mahidol University

Phyathai, 10400, Thailand

RECRUITING

Local Institution - 401

Izmir, 35100, Turkey (Türkiye)

COMPLETED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

beta-Thalassemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; 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 Study Connect Contact Center www.BMSStudyConnect.com

CONTACT

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

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

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 29, 2019
• Study Start: November 7, 2019
• Primary Completion (Estimated): July 2, 2027
• Study Completion (Estimated): June 11, 2035
• Last Updated: January 6, 2026

Record last verified: 2026-01

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

IT (4); CN (6); IN (6); TH (3); TU (1); DE (2); LE (1); US (2); GR (1)