A Phase 2 Study for the Treatment of Anemia with Alpha (α)-Thalassemia to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) in Adults and Evaluate the Safety and Pharmacokinetics in Adolescents
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Celgene Corp.
- Enrollment
- 41
- Locations
- 9
- Primary Endpoint
- Adult cohorts, Primary endpoints: - TD: 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.
Overview
Brief Summary
Adult cohorts: To compare the erythroid response of luspatercept plus BSC vs placebo plus BSC on anemia in participants with A-THAL HbH disease. Adolescent cohorts: To confirm the recommended safe and tolerable dose of luspatercept in adolescent participants with A-THAL
Eligibility Criteria
- Ages
- 0 years to 65+ years (18-64 Years, 0-17 Years, 65+ Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence defined as: - TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization and no transfusion-free period for > 56 days during the 24 weeks prior to randomization - NTD participant: < 6 RBC units during the 24 weeks prior to randomization and, RBC transfusion-free during at least 8 weeks prior to randomization and, mean baseline Hb ≤ 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. Adolescent participant 12 years to < 18 years with documented diagnosis of α- thalassemia HbH disease with transfusion dependence defined as: - TD participant: ≥ 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years - NTD participant: < 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded. - Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.
Exclusion Criteria
- •Key Exclusion Criteria - Adult and Adolescent participants: - Medical Conditions: Diagnosis of α-thalassemia Trait, Hb Bart hydrops, ATRx α-thalassemia, hemoglobin S/β-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. Bleeding disorders manifested by frequent bleeding episodes. Undergone episodes of hemolysis not related to α-thalassemia within the 8 weeks prior to randomization. - Reproductive Status: Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding. - Prior/Concomitant Therapy: Prior exposure to gene therapy to treat α-thalassemia. Undergone hematopoietic stem cell transplantation (HSCT)
Outcomes
Primary Outcomes
Adult cohorts, Primary endpoints: - TD: 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.
Adult cohorts, Primary endpoints: - TD: 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.
Adult cohorts, Primary endpoints: - NTD: 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 RBC transfusion.
Adult cohorts, Primary endpoints: - NTD: 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 RBC transfusion.
Adolescent cohorts, Primary endpoints: - Dose-limiting toxicities (DLTs) defined as observance of ≥ Grade 3-related hemolytic crises or ≥ Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy. - PK parameters - Frequency, severity, and seriousness of AEs
Adolescent cohorts, Primary endpoints: - Dose-limiting toxicities (DLTs) defined as observance of ≥ Grade 3-related hemolytic crises or ≥ Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy. - PK parameters - Frequency, severity, and seriousness of AEs
Secondary Outcomes
No secondary outcomes reported
Investigators
GSM-CT
Scientific
Celgene Corp.