NCT03342404

A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Adults With Non-Transfusion Dependent Beta (β)-Thalassemia (The BEYOND™ Study)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 145 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults with non-transfusion dependent beta (β)-thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP), Open-label Phase (OLP), and Post-Treatment Follow-up Period (PTFP). It is planned to randomize approximately 150 subjects at a 2:1 ratio of luspatercept versus placebo.

Detailed description

The primary objective is: \- To evaluate the effect of luspatercept (BMS-986346) versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval, from Week 13 to Week 24, compared to baseline. The secondary objectives are: * To evaluate the effect of luspatercept versus placebo in anemia-related symptoms in participants with β-thalassemia, as measured by non-transfusion dependent β-thalassemia-patient reported outcome (NTDT-PRO) over continuous 12-week intervals (from Weeks 13 to 24 and from Weeks 37 to 48) compared to baseline. * To evaluate the effect of luspatercept versus placebo on functional and health-related quality of life (QoL) as measured by Medical Outcomes Study 36-Item Short Form (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires * To evaluate the long-term effect of luspatercept versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval from Week 37 to Week 48, compared to baseline * To evaluate the effect of luspatercept versus placebo on iron overload, as measured by liver iron concentration (LIC) and iron chelation therapy (ICT) daily dose * To evaluate the effect of luspatercept versus placebo on iron overload, as measured by serum ferritin * To evaluate the duration of erythroid response * To evaluate the effect of luspatercept versus placebo on physical activity measured by 6-minute walk test (6MWT) Safety and Pharmacokinetics (PK) Objectives * To evaluate safety and tolerability of luspatercept, including immunogenicity * To evaluate population pharmacokinetics (PK) of luspatercept in subjects with β-thalassemia The exploratory objectives are: * To evaluate the effect of luspatercept versus placebo on measures of extra-medullary hematopoietic (EMH) masses, bone mineral density, splenomegaly, pulmonary hypertension, and leg ulcers, when present * To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the NTDT severity score system * To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the Morbidity-free Survival parameters * To examine the relationship of baseline and change in serum Growth Differentiation Factor 11 (GDF11) and other related biomarkers with response to treatment with luspatercept * To examine the effect of luspatercept on fetal hemoglobin (HbF) * To examine the effect of luspatercept on Health Resource Utilization (HRU)

Conditions

• Thalassemia

Interventions

Type	Name	Description
DRUG	Luspatercept	Subjects will start with luspatercept at 1 mg/kg dose level every 3 weeks and can be dose escalated up to 1.25 mg/kg.
OTHER	Placebo	Placebo, Subcutaneous, every 21 days
OTHER	Best Supportive Care (BSC)	Best Supportive Care (BSC)

Timeline

• Start date: 2018-02-05
• Primary completion: 2022-11-28
• Completion: 2022-11-28
• First posted: 2017-11-17
• Last updated: 2023-12-20
• Results posted: 2021-11-18

Locations

16 sites across 6 countries: United States, Greece, Italy, Lebanon, Thailand, United Kingdom

Regulatory

• FDA-regulated drug study