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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03136185
Registration number
NCT03136185
Ethics application status
Date submitted
18/04/2017
Date registered
2/05/2017
Date last updated
10/01/2024
Titles & IDs
Public title
Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)
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Scientific title
A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients With Myelofibrosis
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Secondary ID [1]
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IMG-7289-CTP-102
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Secondary ID [2]
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IMG-7289-CTP-102
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis
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Post-polycythemia Vera Myelofibrosis (PPV-MF)
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Post-essential Thrombocythemia Myelofibrosis (PET-MF)
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Primary Myelofibrosis (PMF)
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Condition category
Condition code
Blood
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Haematological diseases
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Blood
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Other blood disorders
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Musculoskeletal
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Other muscular and skeletal disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Cancer
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Leukaemia - Chronic leukaemia
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Bomedemstat
Experimental: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d - In the Phase 1/2a portion of the study, PMF participants received 0.25 mg/kg/d bomedemstat orally every day (qd) for 85 days during the Initial Treatment Period (ITP). Qualifying participants could continue to receive treatment for an additional 85 days during an Additional Treatment Period (ATP) as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d - In the Phase 1/2a portion of the study, PPV-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d - In the Phase 1/2a portion of the study, PET-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PMF: Bomedemstat 0.5 mg/kg/d - In the Phase 2b portion of the study, PMF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d - In the Phase 2b portion of the study, PPV-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d - In the Phase 2b portion of the study, PET-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PMF: Bomedemstat 0.6 mg/kg/d - In the Phase 2b portion of the study, PMF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d - In the Phase 2b portion of the study, PPV-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Experimental: Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d - In the Phase 2b portion of the study, PET-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Treatment: Drugs: Bomedemstat
Oral (capsule) administration according to dose allocation.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Dose Limiting Toxicities (DLTs)
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Assessment method [1]
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DLT was defined as any one of the following adverse events (AEs) that occured through Day 7 of the Initial Treatment Period (ITP) and was considered by the Investigator to be possibly, probably or definitely related to bomedemstat:
Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding event or the need for prophylactic transfusions)
A clinically significant bleeding event in a participant with a platelet count >50 x 10^9/L (50 k/µL)
Any Grade 4 or 5 non-haematologic adverse event
Any Grade 3 non-haematologic adverse event with failure to recover to Grade 2 within 7 days of drug cessation, with the following exceptions: = Grade 3 nausea, vomiting or diarrhea that responds to standard medical care; = Grade 3 aesthenia lasting less than 14 days; any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 24 hours.
The number of participants with a DLT were reported.
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Timepoint [1]
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Up to Day 7 of the ITP
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Primary outcome [2]
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Number of Participants With Serious Adverse Events
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Assessment method [2]
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An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. Serious AEs (SAEs) were any AE that resulted in death, life-threatening experience, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly, or important medical events. The number of participants with at least one treatment-emergent (TE) SAE was reported for each arm.
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Timepoint [2]
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Up to approximately 30 months
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Primary outcome [3]
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Number of Participants With Adverse Events
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Assessment method [3]
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An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants with at least one TE AE was reported for each arm.
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Timepoint [3]
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Up to approximately 30 months
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Primary outcome [4]
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Number of Participants That Discontinued Study Treatment Due To AEs
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Assessment method [4]
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An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants that discontinued study treatment with bomedemstat due to a TE AE was reported for each arm.
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Timepoint [4]
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Up to approximately 29 months
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Primary outcome [5]
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Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat
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Assessment method [5]
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Cmax was defined as the maximum observed concentration after administration obtained directly from the concentration time profile. Blood and plasma samples were collected at pre-specified timepoints to calculate Cmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
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Timepoint [5]
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Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
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Primary outcome [6]
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Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat
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Assessment method [6]
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Tmax was defined as the time to maximum concentration after administration obtained by inspection. Blood and plasma samples were collected at pre-specified timepoints to calculate Tmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
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Timepoint [6]
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Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
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Primary outcome [7]
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Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24)
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Assessment method [7]
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AUC0-24 was defined as the area under the concentration versus time curve calculated using the linear trapezoidal rule from the zero time-point to the 24-hour time-point concentration. Blood and plasma samples were collected at pre-specified timepoints to calculate AUC0-24 in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
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Timepoint [7]
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Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
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Primary outcome [8]
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Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration
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Assessment method [8]
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CL/F was defined as the apparent total clearance of drug after oral administration. Blood and plasma samples were collected at pre-specified timepoints to calculate CL/F in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
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Timepoint [8]
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Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
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Primary outcome [9]
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Percentage Change From Baseline in Spleen Volume
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Assessment method [9]
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Change in spleen volume was assessed based on calculated spleen volume (ml) measured by magnetic resonance imaging (MRI), or computerized tomography (CT) scan (where locally permitted) if the participant was not a candidate for MRI from Day 0. Percentage change from baseline in spleen volume was reported at Initial Treatment Period (ITP) Day 84, ITP Day 168, Additional Treatment Period 1 (ATP1) Day 84 (Study Day 253), and ATP1 Day 168 (Study Day 337).
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Timepoint [9]
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Baseline, ITP Day 84 (Study Day 84), ITP Day 168 (Study Day 168), ATP1 Day 84 (Study Day 253), and ATP1 Day 168 (Study Day 337)
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Primary outcome [10]
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Percentage Change From Baseline in Spleen Size
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Assessment method [10]
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Change in spleen size was assessed based on spleen palpation (in cm) at each visit. Percentage change from baseline in spleen size was reported at ITP Day 84, ITP Day 168, ATP1 Day 84 (Study Day 253), ATP1 Day 168 (Study Day 337), ATP2 Day 84 (Study Day 422), ATP2 Day 168 (Study Day 506), and ATP3 Day 84 (Study Day 591). As prespecified by the Statistical Analysis Plan, assessments for the Phase 1/2 groups were summarized using visit windowing after the Day 84 visit of the ITP to allow for comparison with the Phase 2b groups at ITP Day 168.
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Timepoint [10]
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Baseline, ITP Day 84 (Study Day 84), ITP Day 168 (Study Day 168), ATP1 Day 84 (Study Day 253), ATP1 Day 168 (Study Day 337), ATP2 Day 84 (Study Day 422), ATP2 Day 168 (Study Day 506), and ATP3 Day 84 (Study Day 591)
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Eligibility
Key inclusion criteria
- >18 years of age
- Diagnosis of either PMF per World Health Organization (WHO) diagnostic criteria for
myeloproliferative neoplasms, or PPV-MF or PET-MF per the International Working Group
for Myelofibrosis Research and Treatment
- High or intermediate-2 risk disease
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Receiving other treatments for the condition (with exceptions and time limits)
- Major surgery in last 4 weeks, any surgery in the last 2 weeks
- History of, or scheduled, hematopoietic stem cell transplant within 24 weeks of
Screening
- History of splenectomy
- Current use of prohibited medications
- A concurrent second active and nonstable malignancy
- Known human immunodeficiency virus infection or active Hepatitis B or Hepatitis C
virus infection
- Other hematologic/biochemistry requirements, as per protocol
- Use of an investigational agent within last 14 days
- Pregnant or lactating females
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
18/07/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
8/03/2022
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Sample size
Target
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Accrual to date
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Final
90
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Recruitment in Australia
Recruitment state(s)
SA
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Recruitment hospital [1]
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Royal Adelaide Hospital - Adelaide
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Recruitment postcode(s) [1]
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- Adelaide
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Michigan
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Country [2]
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Germany
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State/province [2]
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Essen
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Country [3]
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Italy
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State/province [3]
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Florence
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United Kingdom
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State/province [4]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a Phase 1/2 open-label study to evaluate the safety, tolerability, steady-state
pharmacokinetic (PK) and pharmacodynamics (PD) of a lysine-specific demethylase 1 (LSD1)
inhibitor, bomedemstat (IMG-7289/MK-3543), administered orally once daily in participants
with myelofibrosis.
The primary hypothesis is that bomedemstat is a safe and tolerable orally available agent
when administered to participants with myelofibrosis including primary myelofibrosis (PMF),
post-polycythaemia vera-myelofibrosis (PPVMF), and post-essential
thrombocythaemia-myelofibrosis (PET-MF) (collectively referred to as 'MF'); inhibition of
LSD1 by bomedemstat will reduce spleen size in those with splenomegaly, improve
haematopoiesis and reduce constitutional symptoms associated with these disorders.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03136185
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03136185
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