Extension Study of Bomedemstat (IMG-7289/MK-3543) in Participants With Myeloproliferative Neoplasms (IMG-7289-CTP-202/MK-3543-005)

Primary Myelofibrosis Clinical Trial

Official title:

A Multi-Center, Open Label, Extension Study Evaluating the Safety and Efficacy of Bomedemstat for the Treatment of Patients With Myeloproliferative Neoplasms (MPNs) Enrolled in a Prior Bomedemstat Clinical Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05223920
• Other study ID #: IMG-7289-CTP-202
• Secondary ID: MK-3543-0052021-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 16, 2021
• Est. completion date: August 22, 2024

Study information

• Verified date: March 2024
• Source: Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, open-label extension study to assess the long-term safety and efficacy of bomedemstat (MK-3543, formerly called IMG-7289) administered orally once daily in participants with an MPN who participated in a prior bomedemstat study such as, but not limited to, IMG-7289-CTP-102 and IMG-7289-CTP-201 (referred to hereafter as 'feeder studies').

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: August 22, 2024
• Est. primary completion date: August 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Completed at least one Treatment Period (TP) in a prior bomedemstat MPN protocol (such as, but not limited to, IMG-7289-CTP-102 or IMG-7289-CTP-201).

2. In the estimation of the Investigator, the risk-benefit favors continued dosing with bomedemstat.

Exclusion Criteria:

1. Ongoing participation in another investigational study (except observational studies).

2. A history of non-compliance in a prior bomedemstat study (excluding dose suspensions that were medically warranted).

3. Current use of a prohibited medication (e.g., romiplostim).

4. Medical, psychiatric, cognitive, or other conditions that, in the Investigator's opinion, compromise the patient's safety, ability to give informed consent, or comply with the trial protocol.

5. Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.

6. Women of childbearing potential (WOCBP) and fertile men unwilling to agree to use an approved method of contraception from time of enrollment until 14 days after last bomedemstat dose.

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Neoplasms
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Bomedemstat
Capsule (oral)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Gold Coast Hospital and Health Service	Southport	Queensland
Germany	Universittsklinikum Essen	Essen
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	Azienda Ospedaliera SS. Antonio	Alessandria
Italy	Azienda Ospedaliero-Universitaria Careggi - S.O.D. Ematologia (CRIMM)	Firenze
Italy	Azienda Ospedaliero Universitaria di Bologna	Pavia
Italy	Ospedale di Circolo-a Fondazione Macchi	Varese	VA
New Zealand	Middlemore Clinical Trials	Papatoetoe	Aukland
New Zealand	Waitemata District Health Board	Takapuna	Aukland
United Kingdom	Guy's and Saint Thomas' NHS Foundation Trus	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Miami Leonard M. Miller	Miami	Florida
United States	UMPC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Hong Kong,  Italy,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participant-reported Symptom Burden Response Rate on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score (TSS)	The MPN-SAF is a questionnaire to assess symptoms including fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Participant responses for each symptom is scored on an 11-point scale (0 = absent/as good as it can be to 10 = worst imaginable/as bad as it can be). The MPN-SAF TSS is the summation of all the individual scores on a 100-point scale. The participant-reported symptom burden response rate will be assessed as the change from baseline in the percentage of participants who achieve a =50% reduction to the MPN-SAF TSS.	Baseline and up to approximately 3 years
Other	MF Participants: Objective Response Rate (ORR)	ORR is the percentage of participants with Complete Response (CR) or Partial Response (PR) per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) response criteria. For MF participants, CR is, in bone marrow: age-adjusted normocellularity, <5% blasts; =grade 1 MF AND hemoglobin (Hb) =100 g/L and	Up to approximately 3 years
Other	MF Participants: Duration of Response (DOR)	For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented progressive disease (PD) or death. For MF participants, PD is the appearance of a new splenomegaly that is palpable at least 5 cm below the left costal margin (LCM) OR a =100% increase in palpable distance, below LCM, for baseline splenomegaly of 5-10 cm OR a 50% increase in palpable distance, below LCM, for baseline splenomegaly of >10 cm OR leukemic transformation confirmed by a bone marrow blast count of =20% OR a peripheral blood blast content of =20% associated with an absolute blast count of =1 x 109/L that lasts for at least 2 weeks.	Up to approximately 3 years
Other	ET Participants: ORR	ORR is the percentage of participants with CR or PR per IWG-MRT and ELN response criteria. For ET participants, CR is durable resolution of disease-related signs, AND platelet count =400 x 10^9/L, WBC count <10 x 10^9/L, absence of leukoerythroblastosis, AND without signs of progressive disease, and absence of any hemorrhagic or thrombotic events, AND bone marrow histological remission. For ET participants, PR is all CR criteria WITHOUT bone marrow histological remission.	Up to approximately 3 years
Other	ET Participants: DOR	For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented PD or death. For ET participants, PD is transformation into PV, post-ET myelofibrosis, myelodysplastic syndrome, or acute leukemia.	Up to approximately 3 years
Other	Change from Baseline in Spleen Size	Spleen size will be measured by palpation at pre-specified timepoints. The change from baseline in spleen size will be presented.	Baseline and up to approximately 3 years
Other	Change from Baseline in the Mutant (Variant) Allele Burden	Mutant (variant) allele burden will be assessed by genetic testing of germline samples, peripheral blood, and bone marrow at pre-specified timepoints. The change from baseline in the mutant allele burden will be presented.	Baseline and up to approximately 3 years
Other	Change from Baseline in Complete Blood Count (CBC)	CBC will include red and white blood cell (RBC and WBC) and circulating blast cell counts. Blood samples will be taken at pre-specified timepoints to determine CBC. The change from baseline in CBC will be presented.	Baseline and up to approximately 3 years
Other	ET Participants Only: Change from Baseline in the Patient Global Impression of Change (PGIC) Score	The PGIC is a single-score questionnaire and is scored on a scale of 1 to 7. A higher score indicates a worse outcome. The changes from baseline in the PGIC score will be reported.	Baseline and up to approximately 3 years
Other	ET Participants Only: Number of Participants who Experience a Thrombotic or Hemorrhagic Event	The number of participants who experience a thrombotic or hemorrhagic event will be reported	Baseline and up to approximately 3 years
Primary	Number of Participants who Experience an Adverse Event (AE)	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.	Up to approximately 3 years
Primary	Number of Participants who Experience a Serious Adverse Event (SAE)	An SAE is defined as any AE, whether or not related to the study drug, which results in the following outcomes: Death; Life-threatening experience; Required or prolonged inpatient hospitalization; Persistent or significant disability/incapacity; Congenital anomaly; Important medical events that, based upon appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to approximately 3 years
Primary	Number of Participants with Clinically Significant Change from Baseline in One or More Vital Signs	Vital signs will include resting heart rate, semi-supine systolic/diastolic blood pressure, respiratory rate and body temperature. Clinical significance will be determined by the investigator.	Baseline and up to approximately 3 years
Primary	Number of Participants with Clinically Significant Changes from Baseline in One or More Laboratory Parameters	Laboratory investigation will include hematology, coagulation, clinical chemistry and urinalysis. Clinical significance will be determined by the investigator.	Baseline and up to approximately 3 years
Primary	Myelofibrosis (MF) Participants Only: Change from Baseline in Spleen Volume	Spleen volume will be assessed by magnetic resonance imaging (MRI) (or computed tomography [CT] where applicable) at pre-specified timepoints. Change from baseline in spleen volume will be reported.	Baseline and up to approximately 3 years
Primary	Essential Thrombocythemia (ET) Participants Only: Change from Baseline in Platelet Counts	Blood samples will be collected at pre-specified timepoints to determine platelet counts. Change from baseline in platelet counts will be reported.	Baseline and up to approximately 3 years

External Links

•   Merck Clinical Trials Information