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

Imago BioSciences

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: Bomedemstat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03136185

MK-3543-002 (Other Identifier)

2018-003811-23 (EudraCT Number)

IMG-7289-CTP-102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

90 participants in 9 patient groups

Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PMF: Bomedemstat 0.5 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PMF: Bomedemstat 0.6 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d

Experimental group

Description:

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.

Treatment:

Drug: Bomedemstat

Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d

Experimental group

Description:

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:

Drug: Bomedemstat