Phase 2 Study of Luspatercept in Adults with Alpha (a)-thalassemia

Phase 1

• Conditions: Alpha (a)-thalassemia; MedDRA version: 20.1Level: LLTClassification code 10054659Term: Thalassemia alphaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-004928-15-GR
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-08-08
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 176

Inclusion Criteria

-Participant has documented diagnosis of a-thalassemia HbH disease (electrophoresis? or high-performance liquid chromatography [HPLC]?based methods for Hb variant analyses are accepted), with or without transfusion dependence; compounded combination with ß-thalassemia is allowed if at least 1 non-mutated ß-chain gene is present
-Transfusion dependence:
•TD participant = 6 RBC units/24 weeks AND no transfusion-free period for > 56 days during the 24 weeks prior randomization
•NTD participant: < 6 RBC units during the 24 weeks prior to randomization, RBC transfusion-free during at least 8 weeks prior to randomization
AND Mean baseline Hb = 10 g/dL
- Participant must be = 18 years of age at the time of signing the informed consent

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 172
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

- Diagnosis of a-thalassemia Trait, Hb Bart hydrops, ATRx a-thalassemia, hemoglobin S/ß-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation
- Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia or any other hemolytic anemias (eg, severe G6PD deficiency, pyruvate kinase deficiency, etc)
- Bleeding disorders manifested by frequent bleeding episodes (eg, menorrhagia, epistaxis, clotting disorders)
- Undergone episodes of hemolysis not related to a-thalassemia, eg, after use of hemolysis predisposing drugs (eg, anti-malarial, nonsteroidal anti-inflammatory drug [NSAID]), within the 8 weeks prior to randomization
- Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding
- Physical and Laboratory Test Findings
a) Platelet count > 1,000 × 109 /L b)
b) Thrombocytopenia with < 70 × 109 /L if not associated with hypersplenism
c)No concurrent or history of severe hepatic disease or histopathological evidence of liver cirrhosis/fibrosis on liver biopsy: i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3× the upper limit of normal (ULN) ii) Albumin < 3 g/dL
d) Heart disease, heart failure as classified by the New York Heart Association (NYHA; see Appendix 6) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of randomization
e)Lung disease, including pulmonary fibrosis or pulmonary hypertension, which are clinically significant (ie, = Grade 3 per NCI-CTCAE version 5.0 [current active minor version])
f)Creatinine clearance < 60 mL/min (per Cockroft-Gault formula) or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 (per modification of diet in renal disease [MDRD] study)
g)Proteinuria = Grade 3 according to NCI-CTCAE version 5.0 (current active minor version) or protein/creatinine ratio > 350 mg/mmol, or albumin/creatinine ratio > 220 mg/mmol
h)Active hepatitis C virus (HCV) infection, as demonstrated by a positive HCV-RNA test of sufficient sensitivity, or active infectious hepatitis B virus (HBV) as demonstrated by the presence of HBsAg and/or HBV DNA-positive, or known positive human immunodeficiency virus (HIV)
- Prior/Concomitant Therapy:
•Treatment with another investigational drug or device = 30 days (or 5 half-lives, whichever is longer) prior to randomization
•Previous exposure to sotatercept (ACE-011) or luspatercept (BMS-986346/ACE-536)
•Use of an erythropoiesis-stimulating agent (ESA) = 24 weeks prior to randomization
•Iron chelation therapy initiated = 24 weeks prior to randomization
•Use of hydroxyurea treatment = 24 weeks prior to randomization
•Prior exposure to gene therapy
•Undergone HSCT

Study & Design

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