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

Thalassemia Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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) ;

Related Conditions & MeSH terms

• Thalassemia

• NCT number: NCT03342404
• Study type: Interventional
• Source: Celgene
• Status: Completed
• Phase: Phase 2
• Start date: February 5, 2018
• Completion date: November 28, 2022