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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04603495




Registration number
NCT04603495
Ethics application status
Date submitted
20/10/2020
Date registered
26/10/2020

Titles & IDs
Public title
Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
Scientific 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
Secondary ID [1] 0 0
2020-001989-10
Secondary ID [2] 0 0
CPI 0610-04
Universal Trial Number (UTN)
Trial acronym
MANIFEST-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Primary Myelofibrosis 0 0
Post-polycythemia Vera Myelofibrosis 0 0
Post-essential Thrombocythemia Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pelabresib
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Placebo

Experimental: Pelabresib + ruxolitinib - Pelabresib monohydrate tablets + ruxolitinib phosphate tablets

Active comparator: Placebo + ruxolitinib - Matching placebo tablets + ruxolitinib phosphate tablets


Treatment: Drugs: 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.

Treatment: Drugs: Ruxolitinib
Ruxolitinib is a JAK inhibitor and a current, approved treatment option for MF.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Splenic Response by Central Reads at Week 24
Timepoint [1] 0 0
24 weeks of treatment
Secondary outcome [1] 0 0
Total Symptom Score Absolute Change From Baseline to Week 24
Timepoint [1] 0 0
24 weeks of treatment
Secondary outcome [2] 0 0
Number of Participants With TSS50 Response at Week 24
Timepoint [2] 0 0
24 weeks of treatment

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
Accrual to date
Final
430
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Icon Cancer Centre - Brisbane
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Peninsula Private Hospital Clinical Trials Unit - Frankston
Recruitment hospital [5] 0 0
USC Clinical Trials Centre Sunshine Coast Haematology and Oncology Clinic - Buderim
Recruitment hospital [6] 0 0
One Clinical Research PTY LTD - Nedlands
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
QLD 4556 - Buderim
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Alabama
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Washington
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Graz
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Constellation Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04603495