Bomedemstat (IMG-7289) Plus Ruxolitinib for Myelofibrosis

NCT05569538 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: IMG-7289-IIS001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, Phase 2 study of bomedemstat (IMG-7289), an inhibitor of lysine-specific demethylase 1 (LSD1), in combination with JAK inhibition (JAKi) in patients with myelofibrosis.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Bomedemstat; Ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs

  24 months

Secondary Outcomes (2)

• Spleen response at 24 weeks

  24 weeks

• Symptom response at 24 weeks

  24 weeks

Study Arms (2)

Cohort A (Patients refractory to, relapsed or intolerant of ruxolitinib):

EXPERIMENTAL

Bomedemstat : The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort A. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10\^9/L. Ruxolitinib: Patients will continue their prior, stable dose of ruxolitinib. This same dose will be continued throughout the study unless dose modification is required because of toxicity.

Drug: Bomedemstat

Cohort B (Cohort B will consist of 10 patients who are JAK inhibitor naïve):

EXPERIMENTAL

Bomedemstat: The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort B. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10\^9/L. Ruxolitinib: Patients will start treatment with ruxolitinib at Initial Treatment Period Cycle 1 Day 1. The starting dose of ruxolitinib will be 10 mg BID. This same dose will be continued throughout the study unless dose modification is required because of toxicity.

Drug: Bomedemstat

Interventions

Bomedemstat DRUG

Bomedemstat will be self-administered orally once daily. In both cohorts, the dose of bomedemstat will be adjusted in each patient based on titration of the patient's platelet count to the target range. Ruxolitinib will be self-administered orally. Both medications will continue uninterrupted in 28-day cycles. Subjects will continue combination treatment through the Initial Treatment Period (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.

Also known as: IMG-7289

Cohort A (Patients refractory to, relapsed or intolerant of ruxolitinib):; Cohort B (Cohort B will consist of 10 patients who are JAK inhibitor naïve):

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A:
• \. Patients refractory to, relapsed or intolerant of ruxolitinib as per one of the below:
• Refractory is defined as \<30% reduction in spleen length or \<10% SVR compared to baseline having received ruxolitinib for ≥12 weeks prior to enrollment, AND on a stable dose for ≥8 weeks prior to starting investigational therapy
• Relapsed is defined as an increase in spleen volume of ≥25% by MRI/CT from nadir, or, ≥100% in palpable spleen length from a baseline of 5 to 10 cm BLCM or, ≥50% increase in spleen length from a baseline spleen length ≥10 cm BLCM
• Intolerance is defined as the development in patients treated with ruxolitinib for ≥28 days of:
• Red blood cell transfusion requirement of 2 units/month for 2 months
• Grade 3 thrombocytopenia, anemia, hematoma, and/or hemorrhage while on ruxolitinib treatment
• Cohort B:
• Patients who are JAK inhibitor naïve, AND:
• Require MF-directed treatment, AND
• Have measurable disease burden including one of the following:
• Disease-related symptoms, determined by a MFSAF or MPN-SAF TSS of ≥10, or at least 2 symptoms with scores ≥3
• Documented splenomegaly by physical exam, with spleen palpated ≥5 cm below the left costal margin
• Both Cohorts A and B:
• Willing and able to provide informed consent

You may not qualify if:

• Those with increased risk of bleeding, including any of the following:
• Activated partial thromboplastin time (aPTT) ≥1.3 x the local upper limit of normal
• International normalized ratio (INR) ≥1.3 x the local upper limit of normal
• Known history of a platelet function disorder
• Other known bleeding disorder that is active at the time of screening (Von Willebrand's disease, dysfibrinogenemia, hemophilia, etc.)
• History of splenectomy or prior splenic irradiation
• Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of bomedemstat
• Current use of monoamine oxidase A and B inhibitors (MAOIs)
• Uncontrolled, active infection
• Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
• Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
• Known HIV infection or known, active hepatitis B or hepatitis C infection
• Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
• Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates participation

Sponsors & Collaborators

• The University of Hong Kong: lead
• Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA): collaborator

Study Sites (1)

Department of Medicine, the University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

bomedemstat

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Harinder Gill, MD

  Department of Medicine, the University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harinder Gill, MD

CONTACT

+852 22554542; gillhsh@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 6, 2022
• Study Start: December 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: May 23, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)