A study to evaluate the benefit and safety of Luspatercept (ACE-536) in adults with Beta-Thalassemia who do not require regular red blood cell tranfusions

Phase 1

• Conditions: on transfusion dependent ß-thalassemia; MedDRA version: 20.0Level: LLTClassification code 10074356Term: Non-transfusion dependent thalassemiaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2015-003225-33-IT
• Lead Sponsor: CELGENE CORPORATIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-02
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Subjects must be = 18 years of age at the time of signing the (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule (eg,not scheduled to receive hematopoietic stem cell transplantation) and
other protocol requirements.
4. Subject must have documented diagnosis of ß-thalassemia or hemoglobin E/ ß-thalassemia. Concomitant alpha globin mutation and/or duplication are allowed.
5. Subject must be non transfusion dependent, defined as 0 to 5 units of RBCs received during the 24-week period prior to randomization. Note: 1
unit defined for this entry criterion as approximately 200 to 350 mL of transfused packed RBCs.
6. Subject must not be on a regular transfusion program and must be RBC transfusion-free for at least = 8 weeks prior to randomization
7. Subject must have mean baseline hemoglobin = 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.
8. Subject must have performance status: Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
9. A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must:
a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
b. Either commit to true abstinence from eterosexual contact (which must be reviewed on a monthly basis and source documented). If a FCBP
engages in sexual activity that may result in a pregnancy, she must 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 half-life of luspatercept based on multiple-dose pharmacokinetics [PK] data) after discontinuation of study therapy.
10. Male subjects must:
a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5
times the mean terminal half-life of luspatercept based on multiple-dose PK data) following IP discontinuation, even if he has undergone a
successful vasectomy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 148
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1.Subject has any significant medical condition,laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.3. Subject has any conCV) infection as demonstrated by apositive HCV-RNA test of sufficient sensitivity, or active infectioushepatitis B as demonstrated by the dition that confounds the ability to interpret data from the study.4 Subject has a diagnosis of hemoglobin S/ß-thalassemia or alpha (a)-thalassemia.5. Subject has active hepatitis C (Hpresence of hepatitis B surface antigen (HBsAG) and/or hepatitis B virus DNA (HBV-DNA) positive, or known positive HIV. Note: Subjects receiving antiviral therapies should have 2 negative HCVRNA test 3 months apart before ICF signature, ie, one test at the end of the anti-viral therapy and second test 3 months following the first test.6.Subject had deep vein thrombosis (DVT) or stroke requiring medical intervention=24 weeks prior to randomization.7.Subjects on chronic anticoagulant therapy are excluded, unless they stopped the treatment at least 28 days prior to randomization.Anticoagulant therapies for prophylaxis and for surgery or high risk procedures as well as low molecular weight heparin forsuperficial vein thrombosis (SVT) and chronic aspirin are allowed before and during the study.8. Subject has received treatment with another investigational drug or device = 28 days prior to randomization.9. Subject had prior exposure to sotatercept or luspatercept.10. Subject has platelet count > 1000 x 10^9/L11. Subjects on iron chelation therapy at the time of ICF signature must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date. ICT can be initiated at any time during treatment and should be used according to the label.12. Subject had Hydroxyurea and ESA treatment = 24 weeks prior to randomization, and no prior gene therapy13. Subject is pregnant or a lactating female.14. Subject has uncontrolled hypertension. Controlled hypertension for this protocol is considered = Grade 1 according to National Cancer Institute Common Terminology for Adverse Events version 4.0 .15. Subject has major organ damage, including:a. Liver disease with ALT>3xupper limit of normal or history/evidence of cirrhosis, as well as presence of masses/tumor detected by ultrasound at screening.b. Heart disease, heart failure as classified by the New York Heart Association classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction (MI) within 6 months of randomization.c. Severe lung disease, including pulmonary fibrosis or pulmonary hypertension, ie, =G3 NCI CTCAE version 4.0 (current active minor version).d. eGFR< 60 ml/min/1.73 m2.16. Subject has received chronic systemic glucocorticoids = 12 weeks prior to randomization17. Subject had major surgery = 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).18. Subject has history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product.19. Subject has received immunosuppressants = 28 days prior to randomization.20. Subject has history or current malignancies unless the subject has been free of the disease for = 5 years. However,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified