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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04603495
Recruitment Status : Active, not recruiting
First Posted : October 26, 2020
Last Update Posted : May 8, 2024
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Drug: Pelabresib Drug: Ruxolitinib Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 430 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: This study has a double-blind design in which patients and investigators are blinded to study drug; study drugs will be packaged identically. All patients will be randomly assigned to either treatment group in a 1:1 ratio. The blind should only be broken in the case of emergency.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 9, 2021
Actual Primary Completion Date : August 23, 2023
Estimated Study Completion Date : December 2027

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Pelabresib + ruxolitinib
Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
 Drug: Pelabresib

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.


Drug: Ruxolitinib
Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.
Active Comparator: Placebo + ruxolitinib
Matching placebo tablets + ruxolitinib phosphate tablets
 Drug: Ruxolitinib
Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.

Drug: Placebo
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.


Outcome Measures
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Primary Outcome Measures :
  1. Splenic response at Week 24 [ Time Frame: 24 weeks of treatment ]
    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.


Secondary Outcome Measures :
  1. Total Symptom Score absolute change from baseline to Week 24 [ Time Frame: 24 weeks of treatment ]
    A key secondary endpoint of the study is the absolute change in Total Symptom Score at Week 24 compared to baseline as measured by the Myelofibrosis Symptom Assessment Form v4.0. A higher Total Symptom Score indicates a higher disease burden and thus a worse outcome.

  2. Total Symptom Score response at Week 24 [ Time Frame: 24 weeks of treatment ]
    A 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04603495


Locations
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Sponsors and Collaborators
Constellation Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04603495    
Other Study ID Numbers: CPI 0610-04
2020-001989-10 ( EudraCT Number )
First Posted: October 26, 2020    Key Record Dates
Last Update Posted: May 8, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Constellation Pharmaceuticals:
Pelabresib
Ruxolitinib
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
 Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders