NCT04717414

An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions

A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK Inhibitor Therapy and Who Require Red Blood Cell Transfusions

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 313 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this Phase 3 study is to evaluate the efficacy and safety of Luspatercept compared with placebo in subjects with myeloproliferative neoplasm (MPN)-associated Myelofibrosis (MF) and anemia on concomitant Janus kinase 2 (JAK2) inhibitor therapy and who require red blood cell count (RBC) transfusions. The study is divided into Screening Period, a Treatment Phase (consisting of a Blinded Core Treatment Period, a Day 169 Response Assessment, a Blinded Extension Treatment Period, and an Open-label Extension Treatment Period), and a Posttreatment Follow-up Period. Following the Day 169 Response Assessment, subjects who did not show clinical benefit will have the option to unblind. Subjects who were on placebo during the Blinded Core Treatment Period will have the opportunity to crossover into the Open-Label Extension Treatment Period and receive Luspatercept.

Detailed description

Permitted Concomitant Medications and Procedures * Subjects are receiving a JAK2 inhibitor for the treatment of MPN-associated MF that is approved in the country where the study is being conducted. JAK2 inhibitors are to be used according to their respective label and as prescribed as part of the subject's standard-of-care therapy as prescribed by their physician prior to study entry. * Best supportive care (BSC) includes, but is not limited to, treatment with transfusions (eg, RBC, platelet, whole blood), ICTs, antibiotic, antiviral and/or antifungal therapy, and nutritional support as needed. * Granulocyte colony-stimulating factors (ie, G-CSF, granulocyte macrophage colony-stimulating factor \[GM-CSF\]) are allowed only in cases of neutropenic fever or as clinically indicated per product label. * Prophylactic antithrombotic therapy is permitted. * Thrombopoietin and platelet transfusions are permitted. * Treatment with systemic corticosteroids is permitted for nonhematological conditions providing the subject is receiving a constant dose equivalent to ≤ 10 mg prednisone during the study. * Administration of attenuated vaccines (eg, influenza vaccine) is allowed if clinically indicated per Investigator discretion. * Iron chelation therapy (ICT) is to be used according to the product label. If the label permits, the ICT dose should be stable during at least the first 24 weeks of IP. Initiation of ICT while within the first 24 weeks of IP should be clinically indicated to treat an AE. Prohibited Concomitant Medications The following concomitant medications are specifically excluded during the course of study treatment: * Cytotoxic, chemotherapeutic, targeted, or investigational agents/therapies (excluding JAK2 inhibitor therapy) * Azacitidine, decitabine, or other hypomethylating agents * Lenalidomide, thalidomide, and pomalidomide * Erythropoietin stimulating agents (ESAs) and other RBC hematopoietic growth factors (eg, IL-3) * Hydroxyurea or other alkylating agents * Androgens (unless given to treat hypogonadism) * Oral retinoids (topical retinoids are permitted) * Arsenic trioxide * Interferon * Anagrelide * Systemic corticosteroids at a dose equivalent to \> 10 mg prednisone * Investigational products for the treatment of MPN-associated MF

Conditions

• Myeloproliferative Disorders
• Myelofibrosis
• Primary Myelofibrosis
• Post-Polycythemia Vera Myelofibrosis
• Anemia

Interventions

Type	Name	Description
DRUG	ACE-536	Subcutaneous Injection
OTHER	Placebo	Subcutaneous Injection

Timeline

• Start date: 2021-02-25
• Primary completion: 2025-05-26
• Completion: 2032-08-18
• First posted: 2021-01-22
• Last updated: 2025-07-10

Locations

185 sites across 26 countries: United States, Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czechia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Lebanon, Poland, Romania, Russia, South Korea, Spain, United Kingdom

Regulatory

• FDA-regulated drug study