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
- Conditions
- Myeloproliferative DisordersMyelofibrosisPrimary MyelofibrosisPost-Polycythemia Vera MyelofibrosisAnemia
- Interventions
- Other: Placebo
- Registration Number
- NCT04717414
- Lead Sponsor
- Celgene
- Brief 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 313
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm: Luspatercept (ACE-536) ACE-536 Luspatercept will be given to participants via subcutaneous injection (administered on Day 1 of each 21-day treatment cycle) Control Arm: Placebo Placebo Placebo starting dose with volume equivalent to experimental arm subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)
- Primary Outcome Measures
Name Time Method Red blood cell-transfusion independence (RBC-TI) ≥ 12 weeks (RBC-TI 12) Up to 24 weeks Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period starting within the first 24 weeks.
- Secondary Outcome Measures
Name Time Method Red blood cell-transfusion independence ≥ 16 weeks (RBC-TI 16) Up to 24 weeks Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period
Duration of Red blood cell-transfusion independence (RBC-TI 12) Up to end of treatment, approximately 3 years Maximum duration of RBC-TI response
Reduction of transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12-week period Up to 24 weeks Proportion of subjects who reduce their transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12-week period
Duration of reduction in transfusion burden Up to end of treatment, approximately 3 years Maximum duration of when RBC-transfusion dependent subjects who reduce their transfusion burden by ≥ 50% and by ≥ 4 units/12 weeks from baseline over any consecutive 12 week period
Red blood cell-transfusion independence ≥ 12 weeks in the treatment period (RBC-TI 12/TP) Up to end of treatment, approximately 3 years Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period
Red blood cell-transfusion independence ≥ 16 weeks in the treatment period (RBC-TI 16/TP) Up to end of treatment, approximately 3 years Proportion of subjects who become RBC-transfusion free over any consecutive 16-week period
Change in RBC transfusion burden Up to 24 weeks Mean change in transfusion burden (RBC units) from baseline
Cumulative duration of RBC-transfusion independence Up to end of treatment, approximately 3 years Cumulative response duration for subjects achieving multiple episodes of RBC-TI 12
Mean Hgb increase ≥ 1 g/dL from baseline over any consecutive 12-week period in absence of RBC transfusions Up to end of treatment, approximately 3 years Proportion of subjects achieving a 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 Up to end of treatment, approximately 3 years Change in serum ferritin
Incidence of Adverse Events (AEs) From screening up to 42 days post last dose Number of participants with adverse events
Transformation to blast phase: Number of subjects who transform into AML Up to approximately 5 years AML = acute myeloid leukemia
Frequency of Antidrug antibodies (ADA) From randomization and up to including 48 weeks post first dose Will be collected for assessment of anti-drug antibodies (ADA) against Luspatercept in serum in all subjects
Pharmacokinetics - Area Under the Concentration-Time Curve (AUC) From randomization and up to including 48 weeks post first dose Measures of luspatercept exposure area under the curve
Pharmacokinetics - Maximum plasma concentration of drug (Cmax) From randomization and up to including 48 weeks post first dose Maximum plasma concentration of drug
Related Research Topics
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Trial Locations
- Locations (208)
University Of California Los Angeles
🇺🇸Los Angeles, California, United States
Local Institution - 135
🇺🇸Orlando, Florida, United States
BRCR Medical Center Inc.
🇺🇸Plantation, Florida, United States
Local Institution - 112
🇺🇸Chicago, Illinois, United States
University Of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Local Institution - 114
🇺🇸Ann Arbor, Michigan, United States
Local Institution - 108
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Pittsburg Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Scroll for more (198 remaining)University Of California Los Angeles🇺🇸Los Angeles, California, United States