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

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ClinicalTrials.gov Identifier: NCT04603495
Recruitment Status : Recruiting
First Posted : October 26, 2020
Last Update Posted : September 21, 2021
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 20, 2020
First Posted Date  ICMJE October 26, 2020
Last Update Posted Date September 21, 2021
Actual Study Start Date  ICMJE November 19, 2020
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2020)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
Total Symptom Score (TSS) response at Week 24 [ Time Frame: 24 weeks of treatment ]
The key secondary endpoint of the study is TSS response, defined as a ≥50% decrease from baseline in TSS as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0, at Week 24.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of CPI-0610 in Myelofibrosis (MF)
Official Title  ICMJE A Phase 3, Randomized, Double-blind, Active-Control Study of CPI-0610 and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients
Brief Summary A Phase 3, randomized, blinded study comparing CPI-0610 and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been exposed previously to Janus kinase inhibitors (JAKi). CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins. Evidence suggests that inhibition of both BET and JAK pathways can result in synergistic reduction of disease and overall improvement in the prognosis of MF.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • Myelofibrosis
  • Primary Myelofibrosis
  • Post-polycythemia Vera Myelofibrosis
  • Post-essential Thrombocythemia Myelofibrosis
Intervention  ICMJE
  • Drug: CPI-0610

    Double-blind treatment (CPI-0610 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).

    CPI-0610 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.
  • Drug: Placebo
    Placebo tablets are designed to match CPI-0610 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 CPI-0610.
Study Arms  ICMJE
  • Experimental: CPI-0610 + ruxolitinib
    CPI-0610 monohydrate tablets + ruxolitinib phosphate tablets
    Interventions:
    • Drug: CPI-0610
    • Drug: Ruxolitinib
  • Active Comparator: Placebo + ruxolitinib
    Matching placebo tablets + ruxolitinib phosphate tablets
    Interventions:
    • Drug: Ruxolitinib
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2020)
310
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Debbie Johnson 617-714-0531 debbie.johnson@constellationpharma.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   France,   Hungary,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04603495
Other Study ID Numbers  ICMJE 0610-04
2020-001989-10 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Constellation Pharmaceuticals
Study Sponsor  ICMJE Constellation Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Constellation Pharmaceuticals
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP