Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

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.

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.

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.

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.

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.

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.

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.

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.

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.

Oral (capsule) administration according to dose allocation.

Bomedemstat

Medical Director

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.

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.

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

A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients With Myelofibrosis

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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

All-Cause Mortality table includes all allocated participants. Serious and Non-serious adverse events (AEs) tables include all allocated participants who received at least 1 dose of study drug.

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 169 days during the Additional Treatment Period (ATP) as determined by the investigator.

Ph 1/2a PMF: 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 169 days during the ATP as determined by the investigator.

Ph 1/2a PPV-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 169 days during the ATP as determined by the investigator.

Ph 1/2a PET-MF: Bomedemstat 0.25 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 the ATP as determined by the investigator.

Ph 2b PMF: 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 the ATP as determined by the investigator.

Ph 2b PPV-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 the ATP as determined by the investigator.

Ph 2b PET-MF: Bomedemstat 0.5 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 the ATP as determined by the investigator.

Ph 2b PMF: 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 the ATP as determined by the investigator.

Ph 2b PPV-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 the ATP as determined by the investigator.

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

In the Phase 1/2a portion of the study, PMF 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 169 days during the ATP as determined by the investigator.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Multiple

Not Reported

Race/Ethnicity, Customized

Senior Vice President, Global Clinical Development

All participants receiving at least one dose of bomedemstat were included in the DLT analysis.

Number of Participants With Dose Limiting Toxicities (DLTs)

All participants receiving at least one dose of bomedemstat were included in the safety analysis.

Number of Participants With Serious Adverse Events

Number of Participants With Adverse Events

Number of Participants That Discontinued Study Treatment Due To AEs

Plasma

Blood

In the Phase 1/2a portion of the study, 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 169 days during the ATP as determined by the investigator.

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

As pre-specified by the PAP, all participants in the Phase 1/2a portion of the study who received bomedemstat and completed a sufficient portion of the study with enough data for the determination of pharmacokinetic parameters were analyzed. For the purposes of the analysis, Phase 1/2a participants were analyzed irrespective of myelofibrosis disorder (PMF, PPV-MF, or PET-MF) per protocol. Phase 2b participants were excluded from this analysis.

Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat

Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat

Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24)

As pre-specified by the PAP, only participants in the Phase 1/2a portion of the study who received bomedemstat and completed a sufficient portion of the study with enough data for the determination of pharmacokinetic parameters were analyzed. For the purposes of the analysis, Phase 1/2a participants were analyzed irrespective of myelofibrosis disorder (PMF, PPV-MF, or PET-MF) per protocol. Phase 2b participants were excluded from this analysis.

Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration

ITP Day 84 (Study Day 84)

ITP Day 168 (Study Day 168)

ATP1 Day 84 (Study Day 253)

ATP1 Day 168 (Study Day 337)

All allocated participants who received at least one dose of treatment and had available spleen volume data.

Percentage Change From Baseline in Spleen Volume

ATP2 Day 84 (Study Day 422)

ATP2 Day 168 (Study Day 506)

ATP3 Day 84 (Study Day 591)

All allocated participants who received at least one dose of treatment and had available spleen size data.

Spots Global Cancer Trial Database for Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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