Efficacy and Safety Study of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions

Official Title

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) ESA in Native Subjects Who Require Red Blood Cell Transfusions

Summary:

The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This is an interventional active-controlled, open-label, randomized Phase 3 study to compare the efficacy and safety of luspatercept (ACE-536) versus epoetin alfa for the treatment of anemia due to IPSS-R very low, low or intermediate risk MDS in ESA naïve subjects who require RBC transfusions. The study is divided into the Screening Period, a Treatment Period and a Post-Treatment Follow-up Period.

Trial Description

Primary Outcome:

• Red Blood Cell Transfusion Independence (RBCTI) for 24 weeks

Secondary Outcome:

• Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG) within 24 weeks
• Mean hemoglobin increase ≥ 1.5 g/dL
• Time to Hematologic improvement - erythroid response (HI-E)
• Duration of HI-E
• Duration of Red blood cell transfusion independence (RBC-TI) ≥ 24 weeks
• RBC-TI for ≥ 84 days
• Duration of RBC-TI ≥ 84 days
• Time to RBC-TI ≥ 84 days
• Time to first Red blood cell (RBC) transfusion
• RBC transfusion burden on treatment
• For subjects with RBC transfusion burden of ≥4 units/8 weeks at baseline:
• RBC-TI during Weeks 4-24
• RBC-TI for a consecutive 24-week period
• The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30)
• The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire
• Adverse Event (AE)
• Pharmacokinetic - AUC
• Pharmacokinetic - Cmax
• Antidrug antibodies (ADA)
• Progression to AML
• Time to AML
• Overall survival

Anemia is considered to be one of the most prevalent cytopenias in patients who have myelodysplastic syndromes, an umbrella term used to describe disorders relating to the ineffective production of red blood cells, white blood cells, and/or platelets. Ranging in severity from mild (asymptomatic) to severe, anemia can result in patients requiring regular red blood cell (RBC) transfusions, which can lead to further complications from iron overload. The goal of this study is to assess the safety and efficacy of luspatercept versus epoetin alfa in anemic patients who are categorized as International Prognostic Scoring System-Revised (IPSS-R) very low, low, or intermediate risk Myelodysplastic syndrome (MDS), are ESA naïve, and require constant RBC transfusions. The design of the study will allow a period of initial randomization of patients into either the luspatercept or epoetin alfa arm, followed by an open-label treatment period. In both treatment arms, best supportive care (BSC) may be used in combination with study treatment when clinically indicated per investigator. Best supportive care includes, but is not limited to, treatment with transfusions, antibiotic, antiviral and/or antifungal therapy, and nutritional support as needed. Best supportive care for this study excludes the use of ESAs outside of the study treatment. Patients should receive treatment up to a minimum of 24 weeks after which an MDS Disease assessment visit is scheduled to assess the response to treatment. Patients who are determined to be experiencing clinical benefit may continue treatment. Continued clinical benefit will be re-assessed every 24 weeks. Once patients are discontinued from study treatment, they will enter a post treatment follow-up period.

View this trial on ClinicalTrials.gov