A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006)

Essential Thrombocythemia Clinical Trial

Official title:

A Phase 3, Randomized, Open-label, Active-Comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543/IMG-7289) Versus Best Available Therapy (BAT) in Participants With Essential Thrombocythemia Who Have an Inadequate Response to or Are Intolerant of Hydroxyurea

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06079879
• Other study ID #: 3543-006
• Secondary ID: 2023-504865-21IM
• Status: Recruiting
• Phase: Phase 3
• Start date: December 31, 2023
• Est. completion date: August 18, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential thrombocythemia (ET) who have an inadequate response to or are intolerant of hydroxyurea.

The primary study hypothesis is that bomedemstat is superior to the best available therapy with respect to durable clinicohematologic response (DCHR).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 18, 2028
• Est. primary completion date: August 18, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms

• Has a bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the European Consensus Criteria for Grading Myelofibrosis

• Has a history of inadequate response to or intolerance of hydroxyurea based on modified European LeukemiaNet (ELN) criteria for hydroxyurea resistance or intolerance: hydroxyurea resistance (or inadequate response) or hydroxyurea Intolerance

• Has an inadequate or loss of response to their most recent prior ET therapy, requiring a change of cytoreductive therapy

• Has a platelet count > 450 × 10^9/L (450k /µL) assessed up to 72 hours before first dose of study intervention

• Has an absolute neutrophil count (ANC) =0.75 × 10^9/L assessed up to 72 hours before first dose of study intervention

• Participants may have received up to 3 prior lines of therapy including hydroxyurea

Exclusion Criteria:

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or lysine demethylase or monoamine oxidase inhibitor (LSDi or MAOi) or the chosen best available therapy (including anagrelide, interferon alfa/pegylated interferon, ruxolitinib, or busulfan) that contraindicates participation

• History of any illness/impairment of GI function that might interfere with drug absorption (eg, chronic diarrhea or history of gastric bypass surgical procedure), confound the study results or pose an additional risk to the individual by participation in the study

• Evidence at the time of Screening of increased risk of bleeding

• History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder

• Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Bomedemstat
Oral Capsule
• Anagrelide
Oral Capsule
• Busulfan
Oral Tablet
• Interferon alfa/pegylated interferon alfa
Subcutaneous Solution
• Ruxolitinib
Oral Tablet

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0001)	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital ( Site 1100)	Camperdown	New South Wales
Australia	Monash Health-Haematology Research ( Site 0006)	Clayton	Victoria
Australia	Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0502)	Melbourne	Victoria
Australia	Royal Perth Hospital-Haematology ( Site 0504)	Perth	Western Australia
Australia	Royal North Shore Hospital ( Site 0003)	St Leonards	New South Wales
Germany	Universitätsklinikum Halle ( Site 0401)	Halle	Sachsen-Anhalt
Hong Kong	Queen Mary Hospital ( Site 1901)	Hksar
Israel	Rambam Health Care Campus ( Site 2102)	Haifa
Israel	Hadassah Medical Center ( Site 0904)	Jerusalem
Israel	Sheba Medical Center ( Site 2101)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0902)	Tel Aviv
Israel	Yitzhak Shamir Medical Center. ( Site 0901)	Zerifin
Italy	Azienda Ospedaliero Universitaria delle Marche ( Site 0302)	Ancona
Italy	Azienda Ospedaliera Universitaria Careggi ( Site 0030)	Firenze	Toscana
Italy	IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0308)	Meldola	Emilia-Romagna
Italy	Ospedale di Circolo e Fondazione Macchi Varese ( Site 2200)	Varese
Japan	Nippon Medical School Hospital ( Site 3608)	Bunkyo-ku	Tokyo
Japan	University of Yamanashi Hospital ( Site 3606)	Chuo	Yamanashi
Japan	Kyushu University Hospital ( Site 3605)	Fukuoka
Japan	University of Miyazaki Hospital ( Site 3609)	Miyazaki
Korea, Republic of	Seoul National University Bundang Hospital-Hematology ( Site 0605)	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 0603)	Seoul
Korea, Republic of	The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 0606)	Seoul
Netherlands	Albert Schweitzer Ziekenhuis, locatie Dordwijk-Internal Medicine ( Site 2302)	Dordrecht	Zuid-Holland
Netherlands	Spaarne Gasthuis - Hoofddorp-Oncology ( Site 2301)	Hoofddorp	Noord-Holland
New Zealand	Aotearoa Clinical Trials ( Site 0050)	Auckland
New Zealand	North Shore Hospital-Department of Haematology ( Site 0051)	Auckland
Poland	Pratia Onkologia Katowice ( Site 0702)	Katowice	Slaskie
Poland	Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S	Kielce	Swietokrzyskie
Spain	HOSPITAL CLÍNIC DE BARCELONA ( Site 2800)	Barcelona	Cataluna
Spain	Hospital Universitario 12 de Octubre ( Site 2806)	Madrid
Spain	Hospital Universitario Ramón y Cajal-Hematology ( Site 2803)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Virgen de la Victoria ( Site 0418)	Malaga
Spain	Hospital Costa del Sol-Hematology Service ( Site 0412)	Marbella	Malaga
Spain	Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0419)	Salamanca
Spain	CHUS - Hospital Clinico Universitario ( Site 0421)	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Doctor Peset ( Site 0411)	Valencia
Taiwan	Chang Gung Memorial Hospital- Chiayi ( Site 3102)	Chiayi City	Chiayi
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 3105)	Tainan
Taiwan	National Taiwan University Hospital ( Site 3101)	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch ( Site 3103)	Taoyuan
United States	Henry Ford Hospital ( Site 3413)	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Durable Clinicohematologic Response (DCHR) Rate	DCHR rate is the percentage of participants with DCHR, defined as a confirmed reduction of platelet count to =400 × 10^9/L, absence of white blood cell (WBC) count elevation to >10 × 10^9/L locally assessed to be due to ET, and the absence of any thrombotic or major hemorrhagic events or disease progression to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) by Week 52.	Up to approximately 52 weeks
Secondary	Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score	The MFSAF v4.0 is a 7-item participant-reported myelofibrosis symptom assessment which asks respondents to report symptom severity at its worst for each of the 7 items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. For this outcome measure, the change from baseline through Week 156 in scores for the individual item of fatigue severity will be presented.	Baseline and pre-specified timepoints through Week 156
Secondary	Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score	The PROMIS F SF-7a is a 7-item participant-reported assessment that measures both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 = never to 5 = always. Change from baseline in PROMIS Fatigue SF-7a through Week 156 will be presented.	Baseline and pre-specified timepoints through Week 156
Secondary	Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0	The MFSAF v4.0 is a 7-item participant-reported myelofibrosis symptom assessment which asks respondents to report symptom severity at its worst for each of the 7 items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. MFSAF total score for all symptoms at baseline through Week 156 will be presented.	Baseline and pre-specified timepoints through Week 156
Secondary	Duration of Clinicohematologic Response (DOCHR)	For participants who demonstrate DCHR, duration of clinicohematologic response 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, thrombotic or major hemorrhagic events or disease progression to MF, MDS or AML.	Up to approximately 52 weeks
Secondary	Duration of Hematologic Remission (DOHR)	For participants who demonstrate hematologic remission, DOHR is defined as the time from the first documented evidence of platelet and WBC counts reduction until platelet or WBC counts increase to above acceptable threshold.	Up to approximately 52 weeks
Secondary	Percentage of Participants with Thrombotic Events	Thrombotic events include but are not limited to new or recurrent acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, thrombotic digital ischemia, or other thrombotic events.	Up to 156 weeks
Secondary	Percentage of Participants with Major Hemorrhagic Events	Major hemorrhagic events include but are not limited to 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 decrease in hemoglobin level of 2 g/dL or more, or leading to transfusion of 2 or more units of whole blood or red cells.	Up to 156 weeks
Secondary	Disease Progression Rate	Disease progression rate is the percentage of participants with disease progression, defined as the transformation to post-essential thrombocythemia myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia as assessed by the adjudication committee. The disease progression rate of participants in each arm will be presented.	Up to approximately 52 weeks
Secondary	Event Free Survival (EFS)	Event free survival (EFS) is defined as the time from randomization to the first documented thrombotic or major hemorrhagic event or disease progression as assessed by the adjudication committee, or death due to any cause, whichever occurs first.	Up to approximately 52 weeks
Secondary	Number of Participants with An Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 180 weeks
Secondary	Number of Participants Discontinuing From Study Therapy Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an adverse event will be presented.	Up to 152 weeks

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary