Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)

NCT ID: NCT03136185

Last Updated: 2024-01-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-18

Study Completion Date

2022-03-08

Brief Summary

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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

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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.

Conditions

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Myelofibrosis Post-polycythemia Vera Myelofibrosis (PPV-MF) Post-essential Thrombocythemia Myelofibrosis (PET-MF) Primary Myelofibrosis (PMF)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

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.

Group Type EXPERIMENTAL

Bomedemstat

Intervention Type DRUG

Oral (capsule) administration according to dose allocation.

Interventions

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Bomedemstat

Oral (capsule) administration according to dose allocation.

Intervention Type DRUG

Other Intervention Names

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IMG-7289 MK-3543 LSD1 inhibitor

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Site Status

Guy's and St Thomas' Hospitals

London, , United Kingdom

Site Status

Countries

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United States Australia Germany Italy United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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IMG-7289-CTP-102

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3543-002

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003811-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IMG-7289-CTP-102

Identifier Type: -

Identifier Source: org_study_id

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