Clinical trial NCT03136185: Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)
Official title: A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Post-polycythemia Vera Myelofibrosis (PPV-MF)
Post-essential Thrombocythemia Myelofibrosis (PET-MF)
Primary Myelofibrosis (PMF)
Keywords: LSD1
Lead sponsor: Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2017-05-02
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This study initiated as a Phase 1/2a study assessing the safety of the starting dose, an 85-day duration of treatment, and the PK and PD effects of bomedemstat, with transition to a Phase 2b study incorporating changes supported by the Phase 1/2a data.

Eligibility criteria: 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

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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 7 of the ITP
measure: Number of Participants With Serious Adverse Events
timeFrame: Up to approximately 30 months
measure: Number of Participants With Adverse Events
timeFrame: Up to approximately 30 months
measure: Number of Participants That Discontinued Study Treatment Due To AEs
timeFrame: Up to approximately 29 months
measure: Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat
timeFrame: Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
measure: Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat
timeFrame: Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
measure: Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24)
timeFrame: Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
measure: Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration
timeFrame: Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.
measure: Percentage Change From Baseline in Spleen Volume
timeFrame: 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)
measure: Percentage Change From Baseline in Spleen Size
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospitals
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: