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

Constellation Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Primary Myelofibrosis

Treatments: Drug: Placebo; Drug: Pelabresib; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04603495

CPI 0610-04

2020-001989-10 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 430 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

430 participants in 2 patient groups

Pelabresib + ruxolitinib

Experimental group

Description:

Pelabresib monohydrate tablets + ruxolitinib phosphate tablets

Treatment:

Drug: Ruxolitinib

Drug: Pelabresib

Placebo + ruxolitinib

Active Comparator group

Description:

Matching placebo tablets + ruxolitinib phosphate tablets

Treatment:

Drug: Ruxolitinib

Drug: Placebo