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A Study to Evaluate Safety and Efficacy of Bomedemstat (MK-3543-017)

Phase 3
Recruiting
Conditions
Thrombocythemia, Essential
Primary Myelofibrosis
Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Polycythemia Vera
Interventions
Registration Number
NCT06351631
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data. The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have shown the following criteria:

* Participants from the IMG-7289-202/MK-3543-005 (NCT05223920) study must have received at least 6 months of treatment with bomedemstat;

* Essential thrombocythemia (ET) and polycythemia vera (PV) participants from studies other than IMG-7289-202/MK-3543-005 must have achieved confirmed hematologic remission.

No hypothesis testing will be conducted in this study.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
400
Inclusion Criteria
  • Is from a bomedemstat study sponsored by Imago BioSciences, Inc. (a subsidiary of Merck & Co., Inc.) or MSD, and established by the Sponsor as MK-3543-017 ready
  • Has received at least 6 months of treatment with bomedemstat in the IMG-7289-202/MK-3543-005 study, while safely tolerating bomedemstat, and receiving clinical benefit from its use in the estimation of the investigator
  • ET and PV participants from established feeder studies other than IMG-7289- 202/MK-3543-005 must have achieved confirmed hematologic remission, must be safely tolerating bomedemstat, and must be receiving clinical benefit from its use in the estimation of the investigator
  • Is not currently on a dose hold
  • Participant must be able to swallow oral medication and follow instructions for at-home dosing of bomedemstat
Exclusion Criteria
  • Has received prohibited concomitant medications
  • Ongoing or planned participation in another investigational study
  • Has noncompliance in prior bomedemstat study receiving <90% of assigned doses excluding suspensions or holds as assigned by the investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BomedemstatBomedemstatParticipants will receive oral capsules of bomedemstat once daily for up to 10 years, with the starting dose as the same dose that the participant was on at the time of transition from the feeder study.
Primary Outcome Measures
NameTimeMethod
Percentage of participants with one or more adverse events (AEs)Up to ~10 years

An AE is any undesirable physical, psychological or behavioral effect experienced by a patient during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any untoward signs or symptoms experienced by the patient from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants with AEs will be presented.

Percentage of participants who discontinued study treatment due to an AEUp to ~10 years

An AE is any undesirable physical, psychological or behavioral effect experienced by a patient during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any untoward signs or symptoms experienced by the patient from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants who discontinued study treatment due to an AE will be presented.

Secondary Outcome Measures
NameTimeMethod
For participants with ET or PV: Duration of clinicohematologic responseUp to ~10 years

For participants who showed durable clinicohematologic response (DCHR) in their feeder studies, duration of clinicohematologic response is defined as the time from the first documented evidence of confirmed reduction of platelet and white blood cell (WBC) count until confirmed increase of platelet and WBC counts to above acceptable threshold, thrombotic or major hemorrhagic events or disease progression to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The duration of clinicohematologic response will be reported.

For participants with ET or PV: Duration of hematologic remissionUp to ~10 years

For participants who showed confirmed hematologic remission in their feeder studies, duration of hematologic remission is defined as the time from the first documented evidence of confirmed reduction of platelet and WBC count until confirmed increase of platelet and WBC counts to above acceptable threshold. The duration of hematologic remission will be reported.

For participants with ET or PV: Percentage of participants with transformation to MF or MDS/AMLUp to ~10 years

Disease Progression is defined as the transformation to post-ET myelofibrosis (ET participants only), post-PV myelofibrosis (PV participants only), spleen volume increase ≥25% (MF participants only), myelodysplastic syndrome, or acute myeloid leukemia as assessed by the investigator. The percentage of participants with transformation to MF or MDS/AML will be reported.

For participants with MF: Percentage of participants with worsening of splenomegaly or transformation to MDS/AMLUp to ~10 years

Spleen volume will be assessed by magnetic resonance imaging (MRI) (or computed tomography \[CT\] where applicable) at pre-specified timepoints. The percentage of participants with worsening of splenomegaly or transformation to MDS/AML will be reported.

For participants with MF, ET, or PV: Percentage of participants with thrombotic eventsUp to ~10 years

Thrombotic events are defined as: new or recurrent acute myocardial infarction; unstable angina; stroke; transient ischemic attack (TIA); deep venous thrombosis (DVT); pulmonary embolism (PE); thrombotic digital ischemia; other thrombotic events such as peripheral limb ischemia or Budd-Chiari syndrome that are assessed to be due to underlying PV; other vascular occlusive events such as symptoms of cardiac, abdominal or peripheral limb ischemia supported by objective evidence of vessel disease and/or ischemia. The percentage of participants with thrombotic events will be presented.

For participants with MF, ET, or PV: Percentage of participants with major hemorrhagic eventsUp to ~10 years

Hemorrhagic events are defined as: Major Bleeding (MB) Events such as fatal bleeding, and/or symptomatic bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of 2 or more units of whole blood or red cells; Clinically Relevant Non-Major Bleeding (CRNMB) Events Leading to hospitalization or increased level of care or clinically important, prompting a face-to-face medical evaluation. The percentage of participants with major hemorrhagic events will be presented.

For participants with MF, ET, or PV: Event-Free Survival (EFS)Up to ~10 years

EFS is defined as the time from feeder study randomization (if randomized feeder study) or first dose (if nonrandomized feeder study) to the first documented occurrence of thrombotic or major hemorrhagic event or disease progression as assessed by the investigator, or death due to any cause, whichever occurs first. EFS will be reported.

Trial Locations

Locations (16)

DUHS Duke Blood Cancer Center ( Site 6005)

🇺🇸

Durham, North Carolina, United States

University of Michigan ( Site 6000)

🇺🇸

Ann Arbor, Michigan, United States

UPMC Hillman Cancer Center ( Site 6004)

🇺🇸

Pittsburgh, Pennsylvania, United States

Royal Prince Alfred Hospital ( Site 1003)

🇦🇺

Camperdown, New South Wales, Australia

Royal North Shore Hospital ( Site 1001)

🇦🇺

St Leonards, New South Wales, Australia

Gold Coast University Hospital-Cancer and Blood Disorders Clinical Trial Team ( Site 1002)

🇦🇺

Southport, Queensland, Australia

Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 1000)

🇦🇺

Adelaide, South Australia, Australia

Queen Mary Hospital ( Site 1601)

🇭🇰

Hksar, Hong Kong

Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo ( Site 2703)

🇮🇹

Alessandria, Ancona, Italy

Azienda Ospedaliera Universitaria Careggi ( Site 2700)

🇮🇹

Firenze, Toscana, Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 2702)

🇮🇹

Bologna, Italy

Ospedale di Circolo e Fondazione Macchi Varese ( Site 2701)

🇮🇹

Varese, Italy

North Shore Hospital-Department of Haematology ( Site 1401)

🇳🇿

Auckland, New Zealand

Aotearoa Clinical Trials ( Site 1400)

🇳🇿

Auckland, New Zealand

University College London Hospital ( Site 3400)

🇬🇧

London, London, City Of, United Kingdom

Guy's & St Thomas' NHS Foundation Trust ( Site 3401)

🇬🇧

London, London, City Of, United Kingdom

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