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 (INDEPENDENCE)
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ClinicalTrials.gov Identifier: NCT04717414 |
Recruitment Status :
Recruiting
First Posted : January 22, 2021
Last Update Posted : May 3, 2024
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Tracking Information | |||||||||||||||||||||
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First Submitted Date ICMJE | December 29, 2020 | ||||||||||||||||||||
First Posted Date ICMJE | January 22, 2021 | ||||||||||||||||||||
Last Update Posted Date | May 3, 2024 | ||||||||||||||||||||
Actual Study Start Date ICMJE | February 25, 2021 | ||||||||||||||||||||
Estimated Primary Completion Date | March 27, 2025 (Final data collection date for primary outcome measure) | ||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
Red blood cell-transfusion independence (RBC-TI) ≥ 12 weeks (RBC-TI 12) [ Time Frame: Up to 24 weeks ] Proportion of subjects who become RBC-transfusion free over any consecutive 12-week period starting within the first 24 weeks.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||
Change History | |||||||||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||
Descriptive Information | |||||||||||||||||||||
Brief Title ICMJE | 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 ICMJE | 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 | ||||||||||||||||||||
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. |
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Detailed Description | Permitted Concomitant Medications and Procedures
Prohibited Concomitant Medications The following concomitant medications are specifically excluded during the course of study treatment:
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Study Type ICMJE | Interventional | ||||||||||||||||||||
Study Phase ICMJE | Phase 3 | ||||||||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||||||||
Estimated Enrollment ICMJE |
309 | ||||||||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||||||||||
Estimated Study Completion Date ICMJE | August 23, 2025 | ||||||||||||||||||||
Estimated Primary Completion Date | March 27, 2025 (Final data collection date for primary outcome measure) | ||||||||||||||||||||
Eligibility Criteria ICMJE | Subjects must satisfy the following criteria to be randomized in the study: Inclusion Criteria - Subject is ≥18 years of age at the time of signing the ICF.
ii) RBC transfusions are scored in determining eligibility when given for treatment of:. A. Symptomatic (ie, fatigue or shortness of breath) anemia with a pretransfusion Hgb ≤ 9.5 g/dL or. B. Asymptomatic anemia with a pretransfusion Hgb ≤ 7 g/dL. iii) RBC transfusions given for worsening of anemia due to bleeding or infections are not scored in determining eligibility. - Subjects on continuous (eg, absent of dose interruptions lasting ≥ 2 consecutive weeks) JAK2 inhibitor therapy as approved in the country of the study site for the treatment for MPN-associated MF as part of their standard-of-care therapy for at least 32 weeks, on stable daily dose for at least 16 weeks immediately up to the date of randomization and anticipated to be on a stable daily dose of that JAK2 inhibitor for at least 24 weeks after randomization.
ii) Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception** without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) after discontinuation of study therapy. - Male subjects must: Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential** while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy. i) True abstinence is acceptable when it is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.]. ii) Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include: Combined (estrogen and progestogen containing) hormonal contraception: Oral, Intravaginal, Transdermal; Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral, Injectable hormonal contraception, Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence.
Exclusion Criteria
ii) Iron chelation therapy (ICT) is permitted providing the subject is receiving a stable dose for the 8 weeks immediately up to randomization. - Subject with any of the following laboratory abnormalities at screening:. i) Neutrophils: < 1 x 10^9/L. ii) White blood count (WBC): > 100 x 10^9/L. iii) Platelets: the lowest allowable level as approved for the concomitant JAK2 inhibitor but not < 25 x 10^9/L or > 1000 x 10^9/L. iv) Peripheral blood myeloblasts:> 5%. v) Estimated glomerular filtration rate:< 30 mL/min/1.73 m2 (via the 4-variable modification of diet in renal disease [MDRD] formula) or nephrotic subjects (eg, urine albumin-to-creatinine ratio > 3500 mg/g). vi) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT):> 3.0 x upper limit of normal (ULN). vii) Direct bilirubin: ≥ 2 x ULN. A. Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (eg, ineffective erythropoiesis).
ii) Carcinoma in situ of the cervix. iii) Carcinoma in situ of the breast. iv) Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system).
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||||||||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||||||||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czechia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Poland, Romania, Russian Federation, Spain, United Kingdom, United States | ||||||||||||||||||||
Removed Location Countries | Puerto Rico | ||||||||||||||||||||
Administrative Information | |||||||||||||||||||||
NCT Number ICMJE | NCT04717414 | ||||||||||||||||||||
Other Study ID Numbers ICMJE | ACE-536-MF-002 2020-000607-36 ( EudraCT Number ) U1111-1260-9595 ( Registry Identifier: WHO ) |
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Has Data Monitoring Committee | Yes | ||||||||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Celgene | ||||||||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||||||||
Current Study Sponsor ICMJE | Celgene | ||||||||||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||||||||||
Collaborators ICMJE | Not Provided | ||||||||||||||||||||
Investigators ICMJE |
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PRS Account | Celgene | ||||||||||||||||||||
Verification Date | May 2024 | ||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |