Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2) (MANIFEST-2)
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ClinicalTrials.gov Identifier: NCT04603495 |
Recruitment Status :
Active, not recruiting
First Posted : October 26, 2020
Last Update Posted : April 6, 2023
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Condition or disease | Intervention/treatment | Phase |
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Myelofibrosis Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis | Drug: Pelabresib Drug: Ruxolitinib Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 400 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 : | November 19, 2020 |
Estimated Primary Completion Date : | March 2024 |
Estimated Study Completion Date : | April 2027 |

Arm | Intervention/treatment |
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Experimental: Pelabresib + ruxolitinib
Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
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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
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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. |
- 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.
- Total Symptom Score response at Week 24 [ Time Frame: 24 weeks of treatment ]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.

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

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

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: | April 6, 2023 |
Last Verified: | April 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Pelabresib Ruxolitinib |
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 |