Alpha (a)-thalassemia MedDRA version: 20.1 Level: LLT Classification code 10054659 Term: Thalassemia alpha System Organ Class: 100000004850 MedDRA version: 20.1 Level: LLT Classification code 10054659 Term: Thalassemia alpha System Organ Class: 100000004850
Conditions
Sponsors
CELGENE CORPORATION
Eligibility
Sex/Gender
All
Inclusion criteria
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: =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
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 3× the upper limit of normal (ULN) ii) Albumin = Grade 3 per NCI-CTCAE version 5.0 [current active minor version]) f)Creatinine clearance = 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the erythroid response of luspatercept plus BSC vs placebo plus BSC on anemia in participants with a-thalassemia HbH disease;Secondary Objective: To compare the RBC transfusion burden effect of luspatercept plus BSC vs placebo plus BSC in participants with a-thalassemia HbH disease;Primary end point(s): Transfusion dependent Achievement of >= 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Weeks 13-48 compared to the 12-week interval immediately prior to the date of first dose Non-Transfusion dependent Achievement of an increase from baseline of >= 1.0 g/dL in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 in the absence of transfusion;Timepoint(s) of evaluation of this end point: Week 13 to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Transfusion dependent Achievement of = 33% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 24-week interval on treatment compared to the 24-week interval immediately prior to the date of first dose The longest duration with = 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units Number of RBC transfusion units from Week 1 to Week 48 Non-Transfusion dependent Change from baseline to Week 24 in hemoglobin in the absence of transfusion The longest duration of an increase from baseline of = 1.0 g/dL in mean hemoglobin values starting from Week 13 in the absence of transfusion The cumulative time (in weeks) with an increase from baseline of = 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks Achievement of = 3 FACT-An FS score increase from baseline to Week 13 to Week 24;Timepoint(s) of evaluation of this end point: Up to 6 years | — |
Countries
China, Greece, Italy, Taiwan, Thailand, Turkey
Contacts
Public ContactGSM-CT
Bristol-Meyers Squibb International Corporation
Outcome results
None listed