Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)

Study Overview
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Brief Summary
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A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Official Title
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A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients

Conditions
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Myelofibrosis, Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis

Intervention / Treatment
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* Drug: Pelabresib
* Drug: Ruxolitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years Confirmed diagnosis of myelofibrosis (primary, post-polycythemia vera, or post essential thrombocythemia) Adequate hematologic, renal, and hepatic function Have at least 2 symptoms with an average score ≥ 3 or an average total score of ≥ 10 over the 7-day period prior to randomization using the MFSAF v4.0 Prognostic risk-factor score of Intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS) scoring system Spleen volume of ≥ 450 cm^3 Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Exclusion Criteria: Splenectomy or splenic irradiation in the previous 6 months Chronic or active conditions and/or concomitant medication use that would prohibit treatment Had prior treatment with any JAKi or BET inhibitor for treatment of a myeloproliferative neoplasm

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pelabresib + ruxolitinib<br>Pelabresib monohydrate tablets + ruxolitinib phosphate tablets | Drug: Pelabresib<br>* Double-blind treatment (pelabresib or matching placebo) will be administered daily for 14 consecutive days followed by a 7-day break, which is considered 1 cycle of treatment (1 cycle = 21 days). Pelabresib is a small molecule inhibitor of BET proteins with a novel mechanism of action and potential for disease-modifying effects in MF.<br>Drug: Ruxolitinib<br>* Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.<br>|
| Active Comparator: Placebo + ruxolitinib<br>Matching placebo tablets + ruxolitinib phosphate tablets | Drug: Ruxolitinib<br>* Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.<br>Drug: Placebo<br>* Placebo tablets are designed to match pelabresib tablets. Each placebo tablet contains no active pharmaceutical ingredient and is visibly identical to experimental drug in size, shape, and packaging. Placebo dosing follows the same dosing conventions as pelabresib.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Splenic response at Week 24 | The primary endpoint of the study is splenic response, defined as a ≥35% reduction from baseline in spleen volume as measured by magnetic resonance imaging (MRI) or computerized tomography (CT), at Week 24. | 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Symptom Score response at Week 24 | The key secondary endpoint of the study is Total Symptom Score response, defined as a ≥50% decrease from baseline in Total Symptom Score as measured by the Myelofibrosis Symptom Assessment Form v4.0, at Week 24. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome. | 24 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pelabresib, Ruxolitinib