RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2019-11-07

Study Completion:2035-06-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04143724

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:6 Years to 17 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	* 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). * 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.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

* 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).
* 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.

Contacts and Locations

Study Contact

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

Principal Investigator

Bristol-Myers Squibb

STUDY_DIRECTOR

Bristol-Myers Squibb

Study Locations (Sites)

Local Institution - 601

Los Angeles, California, 90027

United States

New York Presbyterian Hospital

New York, New York, 10065-4870

United States

Collaborators and Investigators

Sponsor: Celgene

Bristol-Myers Squibb, STUDY_DIRECTOR, Bristol-Myers Squibb

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-11-07

Study Completion Date2035-06-11

Study Record Updates

Study Start Date2019-11-07

Study Completion Date2035-06-11

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Beta-Thalassemia