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

Official Title

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

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.

Trial Description

Primary Outcome:

• Red blood cell-transfusion independence (RBC-TI) ≥ 12 weeks (RBC-TI 12)

Secondary Outcome:

• Red blood cell-transfusion independence ≥ 16 weeks (RBC-TI 16)
• Duration of Red blood cell-transfusion independence (RBC-TI 12)
• Reduction of transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12-week period
• Duration of reduction in transfusion burden
• Red blood cell-transfusion independence ≥ 12 weeks in the treatment period (RBC-TI 12/TP)
• Red blood cell-transfusion independence ≥ 16 weeks in the treatment period (RBC-TI 16/TP)
• Change in RBC transfusion burden
• Cumulative duration of RBC-transfusion independence
• Mean Hgb increase ≥ 1 g/dL from baseline over any consecutive 12-week period in absence of RBC transfusions
• Change in serum ferritin from baseline
• Incidence of Adverse Events (AEs)
• Transformation to blast phase: Number of subjects who transform into AML
• Frequency of Antidrug antibodies (ADA)
• Pharmacokinetics - Area Under the Concentration-Time Curve (AUC)
• Pharmacokinetics - Maximum plasma concentration of drug (Cmax)

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 the study:

• 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

View this trial on ClinicalTrials.gov