Health Condition 1: D561- Beta thalassemia
Conditions
Interventions
Intervention1: Luspatercept (ACE-536): Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular
domain (ECD) of the human activin receptor IIB (ActRIIB) linked t
Sponsors
Celgene Corporation
Eligibility
Inclusion criteria
Inclusion criteria: Participants must satisfy the following criteria to be enrolled into the study: 1) Participant must be 6 years to less than 18 years of age at the time of signing the informed consent form ICF or informed assent form IAF. 2) Participant (and when applicable, parent/legal representative) must understand and voluntarily sign an ICF/IAF prior to conducting any study-related assessments/procedures. 3) Participant (and when applicable, parent/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements. 4) Participant must have documented diagnosis of β-thalassemia or HbE/β-thalassemia. 5) Transfusion dependence: 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 less than 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 less than or equal to 10 g/dL, based on a minimum of 2 measurements greater than or equal to 1 week apart within 4 weeks prior to enrollment; hemoglobin values within 21 days post-transfusion will be excluded. 6) Participant has Karnofsky age greater than or equal to 16 years or Lansky age less than 16 years performance status score greater than or equal to 50 at screening. 7) Female children of childbearing potential (FCCBP), females of childbearing potential (FCBP), and male 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. 8) 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 FCBP 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 FCCBP/FCBP, including those who commit to complete abstinence. Female children of childbearing potential/FCBP 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/FCBP must agree to ongoing pregnancy testing during the course of the study at the EOT visit and at the 9 week Safety Follow-up visit. • Female part
Exclusion criteria
Exclusion criteria: 1) Participant has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study. 2) Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study. 3) Participant has any condition that confounds the ability to interpret data from the study. 4) Participant has a diagnosis of Hemoglobin S/beta-thalassemia or alpha -thalassemia (eg, Hemoglobin H); beta-thalassemia combined with alpha-thalassemia is allowed. 5) Participant has active hepatitis C (HCV) infection as demonstrated by a positive HCV-ribonucleic acid (RNA) 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. 6) Participant has severe infection less than equal to 28 days prior to enrollment. Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have completely resolved, and based on Investigator assessment in consultation with the Clinical Trial Physician, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment. 7) Participant has received a live COVID-19 vaccine less than equal to 28 days prior to screening. 8) Participant has deep vein thrombosis (DVT), stroke, or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention less than equal to 24 weeks prior to enrollment. 9) Participant has chronic anticoagulant therapy less than equal to 28 days prior to enrollment (Anticoagulant therapies used for prophylaxis for surgery or high risk procedures as well as low molecular weight [LMW] heparin for superficial vein thrombosis and chronic aspirin are allowed) 10) Participant has platelet count greater than 1000 x 10 raise to 9/L. 11) Participant has poorly controlled diabetes mellitus within 24 weeks prior to enrollment as defined by short term (eg, hyperosmolar or ketoacidotic crisis) and/or history of diabetic cardiovascular complications (eg, stroke or myocardial infarction). 12) Participant has treatment with another investigational drug or device less than equal to 28 days prior to enrollment. 13) Participant has prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536). 14) Participant underwent or is scheduled for HSCT or gene therapy. 15) Participant has used an erythropoiesis-stimulating agent (ESA) less than equal to 24 weeks prior to enrollment. 16) Participant use of iron chelation therapy (ICT), if initiated less than equal to 8 weeks prior to enrollment (allowed if initiated more than 8 weeks before or during treatment). 17) Participant use of hydroxyurea treatment less than equal to 24 weeks prior to enrollment. 18) Participant is pregnant or breastfeeding female. 19) Participant has unc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| â?¢ To determine the recommended dose (RD) of luspatercept that is safe and tolerable in pediatric participants with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia â?¢To evaluate the pharmacokinetics (PK) of luspatercept in pediatric participants with TD or NTD β-thalassemia Timepoint: â?¢ Cycle 1 Day 1 up to maximum 1 year post Cycle 1 Day 1 â?¢ Cycle 1 Day 1 up to maximum 1 year post Cycle 1 Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| For TD & NTD β-thalassemia Participants: â?¢ The safety of luspatercept in pediatric participants â?¢ The immunogenicity of luspatercept â?¢ The mean change in mean daily dose of iron chelation therapy (ICT) â?¢ The mean change in serum ferritin For TD β-thalassemia Participants: â?¢ The mean change in red blood cell (RBC) transfusion burden For NTD β-thalassemia Participants: â?¢ The mean change in hemoglobin levels.Timepoint: â?¢ 12 weeks prior to enrollment | — |
Countries
China, Germany, Greece, India, Italy, Lebanon, Thailand, Turkey, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed