Home › Trials › NCT04143724

Evaluating the safety and pharmacokinetics of Luspatercept in children with beta-thalassemia

A Phase 2a Study to Evaluate the Safety and Pharmacokinetics of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia

Phase 2 Interventional Celgene · NCT04143724

This study is testing a new drug called Luspatercept to see if it's safe and how it works in children with beta-thalassemia, starting with teens and then including younger kids.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment99 (estimated)
Ages6 Years to 17 Years
SexAll
SponsorCelgene Industry-sponsored
Drugs / interventionsprednisone
Locations26 sites (Los Angeles, California and 25 other locations)
Trial IDNCT04143724 on ClinicalTrials.gov

What this trial studies

This Phase 2a study investigates the safety and pharmacokinetics of Luspatercept (ACE-536) in pediatric participants diagnosed with beta-thalassemia. The study is divided into two parts: one for transfusion-dependent (TD) participants and another for non-transfusion-dependent (NTD) participants, both involving adolescents aged 12 to under 18 years. Following an evaluation of safety data from Part A, the study will expand to include younger participants aged 6 to under 12 years in Part B. The study aims to assess the drug's effects through dose escalation and expansion cohorts.

Who should consider this trial

Good fit: Ideal candidates for this study are children aged 6 to under 18 years with a documented diagnosis of beta-thalassemia or Hemoglobin E/beta-thalassemia.

Not a fit: Patients who do not have beta-thalassemia or are outside the age range of 6 to under 18 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that improves the management of beta-thalassemia in pediatric patients.

How similar studies have performed: Other studies have shown promise in using similar pharmacological approaches for treating beta-thalassemia, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

* 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.
* Male (as assigned at birth) participants, as appropriate to age and the discretion of the study physician:

  * Must practice true abstinence\* (which must be reviewed on a monthly basis) or agree to use a synthetic or latex condom during sexual contact with a pregnant female or a Female children of childbearing potential (FCCBP)/ IOCBP while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal t1/2 of luspatercept based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy.

    * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the participant. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\] \*\* Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include: Combined (estrogen and progesterone/progestin containing) hormonal contraception: Oral; Intravaginal; Transdermal; Progestogen/progestin only hormonal contraception associated with inhibition of ovulation: Oral; Injectable hormonal contraception; Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence.

Exclusion Criteria

* 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:

  1. Symptomatic splenomegaly
  2. Liver disease with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \> 3X the upper limit of normal (ULN) for age
  3. Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of enrollment
  4. Lung disease, including pulmonary fibrosis or pulmonary hypertension of Grade ≥ 3 according to NCI-CTCAE version 5.0.
  5. Renal insufficiency defined as:
* A serum creatinine based on age/gender based on threshold derived from Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control.
* Participant has proteinuria ≥ Grade 3 according to NCI CTCAE version 5.0 (which is equivalent to a urine protein/creatinine ratio \> 215 mg/mmol of creatinine), or a urine albumin/creatinine ratio \> 129 mg/mmol of creatinine.
* Participant use of high dose long-term therapy with systemic glucocorticoids ≤ 12 weeks prior to enrollment (physiologic replacement therapy for adrenal insufficiency is allowed). Low-dose long-term (defined as ≤ 0.2 mg/kg/day or ≤ 10 mg/day of prednisone equivalent), short treatment (eg, for prevention or treatment of transfusion reactions) inhaled, intranasal and topical corticosteroids are allowed.
* Participant has history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the IP (refer to the IB).
* Participant use of cytotoxic agents, immunosuppressants ≤ 28 days prior to enrollment (ie, antithymocite globulin (ATG) or cyclosporine).
* Participant has history of malignancy with the exception of:

  1. Curatively resected nonmelanoma skin cancer.
  2. Curatively treated carcinoma in situ.
  3. Other solid tumor with no known active disease in the opinion of the Investigator.
* Participant who has extramedullary hematopoiesis (EMH) complications or requires treatment to control the growth of EMH masse(s) during the screening period.
* Participants with any medical or psychiatric condition that in the opinion of the investigator would put the participant at unacceptable risk of participating in the study or may impact interpretation of the study results.
* Participants who use herbs or food supplements (eg: Chinese traditional medicine), if, per investigator's judgment, likely to impact the safety and efficacy assessment, for 24 weeks before initiating the study treatment for TD participants, and 12 weeks for NTD participants.

Where this trial is running

Los Angeles, California and 25 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Beta-ThalassemiaACE-536LuspaterceptPharmacokineticsRed Blood Cell Transfusion
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.