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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06079879




Registration number
NCT06079879
Ethics application status
Date submitted
6/10/2023
Date registered
12/10/2023
Date last updated
26/09/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2023-504865-21
Secondary ID [2] 0 0
3543-006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Essential Thrombocythemia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bomedemstat
Treatment: Drugs - Anagrelide
Treatment: Drugs - Busulfan
Treatment: Drugs - Interferon alfa/pegylated interferon alfa
Treatment: Drugs - Ruxolitinib

Experimental: Bomedemstat - Participants will begin treatment at a dose of 50 mg of bomedemstat daily. Dosage will be adjusted either up or down within specified time parameters for each participant to the dose that provides sufficient exposure to safely inhibit thrombopoiesis to decrease platelet counts to the target range. All participants will be treated daily for up to 52 weeks, and are eligible for an extended treatment phase up to 152 weeks.

Active comparator: Best Available Therapy - Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 152 weeks at the investigators discretion.


Treatment: Drugs: Bomedemstat
Oral Capsule

Treatment: Drugs: Anagrelide
Oral Capsule

Treatment: Drugs: Busulfan
Oral Tablet

Treatment: Drugs: Interferon alfa/pegylated interferon alfa
Subcutaneous Solution

Treatment: Drugs: Ruxolitinib
Oral Tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Durable Clinicohematologic Response (DCHR) Rate
Timepoint [1] 0 0
Up to approximately 52 weeks
Secondary outcome [1] 0 0
Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score
Timepoint [1] 0 0
Baseline and pre-specified timepoints through Week 156
Secondary outcome [2] 0 0
Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score
Timepoint [2] 0 0
Baseline and pre-specified timepoints through Week 156
Secondary outcome [3] 0 0
Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0
Timepoint [3] 0 0
Baseline and pre-specified timepoints through Week 156
Secondary outcome [4] 0 0
Duration of Clinicohematologic Response (DOCHR)
Timepoint [4] 0 0
Up to approximately 52 weeks
Secondary outcome [5] 0 0
Duration of Hematologic Remission (DOHR)
Timepoint [5] 0 0
Up to approximately 52 weeks
Secondary outcome [6] 0 0
Percentage of Participants with Thrombotic Events
Timepoint [6] 0 0
Up to 156 weeks
Secondary outcome [7] 0 0
Percentage of Participants with Major Hemorrhagic Events
Timepoint [7] 0 0
Up to 156 weeks
Secondary outcome [8] 0 0
Disease Progression Rate
Timepoint [8] 0 0
Up to approximately 52 weeks
Secondary outcome [9] 0 0
Event Free Survival (EFS)
Timepoint [9] 0 0
Up to approximately 52 weeks
Secondary outcome [10] 0 0
Number of Participants with An Adverse Event (AE)
Timepoint [10] 0 0
Up to 180 weeks
Secondary outcome [11] 0 0
Number of Participants Discontinuing From Study Therapy Due to an AE
Timepoint [11] 0 0
Up to 152 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/08/2028
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital ( Site 1100) - Camperdown
Recruitment hospital [2] 0 0
Royal North Shore Hospital ( Site 0003) - St Leonards
Recruitment hospital [3] 0 0
Calvary Mater Newcastle ( Site 0505) - Waratah
Recruitment hospital [4] 0 0
Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0001) - Adelaide
Recruitment hospital [5] 0 0
Monash Health-Haematology Research ( Site 0006) - Clayton
Recruitment hospital [6] 0 0
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0502) - Melbourne
Recruitment hospital [7] 0 0
Royal Perth Hospital-Haematology ( Site 0504) - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3021 - Melbourne
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
Argentina
State/province [3] 0 0
Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Tucuman
Country [5] 0 0
Canada
State/province [5] 0 0
New Brunswick
Country [6] 0 0
China
State/province [6] 0 0
Beijing
Country [7] 0 0
China
State/province [7] 0 0
Fujian
Country [8] 0 0
China
State/province [8] 0 0
Guangdong
Country [9] 0 0
China
State/province [9] 0 0
Hebei
Country [10] 0 0
China
State/province [10] 0 0
Hubei
Country [11] 0 0
China
State/province [11] 0 0
Jiangxi
Country [12] 0 0
China
State/province [12] 0 0
Shaanxi
Country [13] 0 0
China
State/province [13] 0 0
Shandong
Country [14] 0 0
China
State/province [14] 0 0
Shanghai
Country [15] 0 0
China
State/province [15] 0 0
Tianjin
Country [16] 0 0
China
State/province [16] 0 0
Zhejiang
Country [17] 0 0
Colombia
State/province [17] 0 0
Antioquia
Country [18] 0 0
Colombia
State/province [18] 0 0
Cordoba
Country [19] 0 0
Colombia
State/province [19] 0 0
Distrito Capital De Bogota
Country [20] 0 0
France
State/province [20] 0 0
Ille-et-Vilaine
Country [21] 0 0
France
State/province [21] 0 0
Indre-et-Loire
Country [22] 0 0
France
State/province [22] 0 0
Lorraine
Country [23] 0 0
France
State/province [23] 0 0
Rhone
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France
State/province [24] 0 0
Paris
Country [25] 0 0
Germany
State/province [25] 0 0
Nordrhein-Westfalen
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Germany
State/province [26] 0 0
Sachsen-Anhalt
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Germany
State/province [27] 0 0
Sachsen
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Hong Kong
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Hksar
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Hungary
State/province [29] 0 0
Budapest
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
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Israel
State/province [31] 0 0
Jerusalem
Country [32] 0 0
Israel
State/province [32] 0 0
Ramat Gan
Country [33] 0 0
Israel
State/province [33] 0 0
Tel Aviv
Country [34] 0 0
Israel
State/province [34] 0 0
Zerifin
Country [35] 0 0
Italy
State/province [35] 0 0
Ferrara
Country [36] 0 0
Italy
State/province [36] 0 0
Forli-Cesena
Country [37] 0 0
Italy
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Lombardia
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Italy
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Toscana
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Italy
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Alessandria
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Italy
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Ancona
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Italy
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Reggio Emilia
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Italy
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Torino
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Italy
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Varese
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Japan
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Ehime
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Ishikawa
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Japan
State/province [48] 0 0
Mie
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Japan
State/province [49] 0 0
Miyagi
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Japan
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Osaka
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Japan
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Tokyo
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Japan
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Yamanashi
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Japan
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Fukuoka
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Japan
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Fukushima
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Japan
State/province [55] 0 0
Miyazaki
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Japan
State/province [56] 0 0
Okayama
Country [57] 0 0
Korea, Republic of
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Kyonggi-do
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Korea, Republic of
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Seoul
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Netherlands
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Noord-Holland
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Netherlands
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Zuid-Holland
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Netherlands
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Groningen
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New Zealand
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Auckland
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Poland
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Slaskie
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Poland
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Swietokrzyskie
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Portugal
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Braga
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Portugal
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Lisboa
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Portugal
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Porto
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Spain
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Barcelona
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Spain
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Cataluna
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Spain
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La Coruna
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Spain
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Madrid, Comunidad De
Country [72] 0 0
Spain
State/province [72] 0 0
Malaga
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Spain
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Albacete
Country [74] 0 0
Spain
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Madrid
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Spain
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Salamanca
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Spain
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Valencia
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Sweden
State/province [77] 0 0
Orebro Lan
Country [78] 0 0
Sweden
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Stockholms Lan
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Edirne
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Turkey
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Istanbul
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Turkey
State/province [83] 0 0
Kocaeli
Country [84] 0 0
Turkey
State/province [84] 0 0
Samsun
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Cambridgeshire
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Newport

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/study/NCT06079879
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharpe & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06079879