None listed
Conditions
Brief summary
This is a study of safety and tolerability of a drug called IMG-7289; also known as bomedemstat. The study will compare the amount of IMG-7289 that is in the blood after taking a single dose of 2 different formulations of IMG-7289, both with food and without food. IMG-7289 is being developed to inhibit an enzyme (LSD1) known to contribute to tumour growth, and may be used as a future treatment for cancers including myeloid leukemia and myelofibrosis. Who is it for? You may be eligible for this study if you are a healthy adult aged 18 to 65 years, have a non-smoker status and have no prior history of relevant drug hypersensitivity. People who have been diagnosed with cancer will not be eligible for this study. Study details In this study participants will test two formulations of IMG-7289 with and without food. In each study period, participants will spend 4 nights in clinic followed by 4 follow-up visits. There will be 4 study periods, with one End of Study outpatient visit. There will be a 14-day washout period between doses to ensure there is no IMG-7289 in their body before the next dose. All participants will be asked to undergo blood tests and answer questions regarding their health. It is hoped that information from this study informs researchers of how the body metabolises IMG-7289 and thus how it may be used to treat bone marrow malignancies, such as myeloid leukemia and myelofibrosis.
Interventions
Sixteen healthy adult volunteers will be enrolled in a total of four treatment arms, four participants in each arm. For each participant enrolled in this study, there will be a total of 4 confinement periods. Each confinement period will commence on Day -1, with dosing on Day 1 and discharge on Day 4. Each participant will be assigned to one of 4 treatment arms in a randomised open label manner crossover study design, with the first 8 participants assigned to arms 1 and 2, and the second 8 parti
Sixteen healthy adult volunteers will be enrolled in a total of four treatment arms, four participants in each arm. For each participant enrolled in this study, there will be a total of 4 confinement periods. Each confinement period will commence on Day -1, with dosing on Day 1 and discharge on Day 4. Each participant will be assigned to one of 4 treatment arms in a randomised open label manner crossover study design, with the first 8 participants assigned to arms 1 and 2, and the second 8 participants assigned to arms 3 and 4. Each participant will be administered a single dose of each treatment: formulation 1 after a high-fat meal), formulation 1 administered fasted, formulation 2 administered after a high-fat meal and formulation 2 administered fasted. The order of administration will be determined by randomisation. Participants will receive a total of four doses of IMG-7289 (a total of 200 mg) on 4 different days and given during 4 separate treatment periods. Formulation 1 is the encapsulated IMG-7289 drug substance; it does not contain any excipients whereas Formulation 2 is a formulated capsule containing the IMG-7289 drug substance with the following excipients: fumaric acid, lactose anhydrous, Avicel DG, and magnesium stearate. For all administrations, a 10-hour overnight fast is required. For the fed administration, a high fat breakfast 30 minutes pre-dose will be required. The participant will be required to stay in the unit for the next three days and three nights following administration to monitor any changes to their health during this time followed by four follow-up visits for each of the study periods. The study periods will be separated by 14-day wash out intervals. The total maximum study duration for participants in this study is 86 days (approximately 13 weeks, including up to 27 days of screening and 59 days of clinical conduct, inclusive of visit windows). The clinical facility staff will administer each study treatment; administration will be verified by a second staff member.
Sponsors
Avance Clinical
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers will be included in this study if they satisfy all the following criteria: 1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. 2. Adult males and females, 18 to 65 years of age (inclusive) at screening. 3. BMI greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight greater than or equal to 55 and less than or equal to 100 kg at screening. 4. Be nonsmokers (including tobacco, e-cigarettes, marijuana or other nicotine containing product) for at least 3 months prior to first study drug administration and have a negative result of cotinine test at screening and on Day -1 for each confinement period. 5. No prior history of chronic alcohol abuse or excessive alcohol intake, at the discretion of the Principal Investigator (PI), within 12 weeks prior to screening, and negative alcohol test results. 6. No prior history of substance abuse or drug addiction within 12 months prior to first study drug administration and negative urine drug screen results at screening and on Day -1 for each confinement period. In the event the urinary drug test is positive, the test may be repeated once (at the discretion of the PI) to confirm eligibility. 7. No prior history of relevant drug hypersensitivity. 8. Medically healthy (in the opinion of the PI) as determined by pre-study medical history and without clinically significant abnormalities at screening and prior to first dose administration on Day 1, including. a. Physical examination without any clinically relevant findings; b. Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine position; c. Heart rate in the range of 45 to 100 beats/minute after 5 minutes rest in supine position; d. Body temperature (tympanic), between 35.5°C and 37.7°C; e. A 12-lead electrocardiogram (ECG) within normal range or with abnormalities that are not hazardous to the participant according to the opinion of the PI; f. No clinically relevant findings in clinical laboratory blood and urinalysis tests as judged by the PI. The above assessments may be repeated once, if abnormal values were recorded in the first instance, at the discretion of the PI. 9. Female participants must: a. Be of nonchildbearing potential b. If of childbearing potential, must have a negative pregnancy test at screening (blood test) and before the first study drug administration (Day -1 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method from signing the consent form until at least 30 days after the last dose of study drug. c. Must not be breast-feeding. 10. Male participants, if not surgically sterilised, must be willing not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must be willing to use a condom in addition to having the female partner use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug. 11. Have suitable venous access for blood sampling. 12. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Exclusion criteria
Healthy volunteers will be excluded from this study if there is evidence of any of the following at screening or after check in prior to dose administration on Day 1 (clinical and laboratory assessments may be repeated once, at the discretion of the PI, in the case of abnormal findings in the first instance): 1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant. 2. Current infection that requires antibiotic, antifungal, antiparasitic or antiviral medications. 3. Any history of malignant disease in the last 5 years (except basal cell skin cancer or squamous cell skin cancer with history of curative treatment and no recurrence for more than 1 year prior to screening). 4. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. 5. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 4 months prior to the first study drug administration. 6. Liver function test results (i.e., aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gammaglutamyl transferase [GGT]) and total bilirubin elevated greater than or equal to 1.5-fold above the normal limits. 7. Abnormal renal function tests, indicated by calculated creatinine clearance less than 80 mL/min, and serum creatinine greater than 1.5-fold of the normal range, respectively. 8. History of bleeding diathesis, thrombocytopenia or other clotting or coagulation disorder. 9. Platelets below the lower limit of normal (150 x 109/L). 10. Family history of long QT syndrome or of unexplained sudden death in a first-degree relative under 50 years of age. 11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies. 12. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 13. Use of any prescription medication within 14 days or 7 half-lives of the medication (whichever is longer) prior to the first study drug administration (except hormonal contraceptives associated with inhibition of ovulation and other medication deemed non-clinically relevant by the PI in consultation with Imago BioSciences). 14. Use of over-the-counter medication excluding routine vitamins and herbal supplements (paracetamol less than 2 grams/day is acceptable) but including mega dose vitamin therapy and St John’s Wort within 7 days of first dosing and throughout the study, unless agreed as non-clinically relevant by the PI. 15. Consumption of caffeine or alcohol, or any products containing grapefruit, Seville orange, star fruit or pomegranate within 48 hours prior to the first IMG-7289 dose administration on Day 1 (consumption is also not permitted within 48 hours of Day 1 for each period). 16. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the PI, would interfere with the volunteer’s ability to participate in the trial. 17. Use of any live vaccinations within 30 days prior to the first study drug administration except for vaccines for influenza. It is noted that mRNA or adeno-associated virus (AAV)-based COVID-19 vaccinations are permitted at any stage throughout the study. 18. Donation of blood or plasma within 60 days prior to first study drug administration, donation of haematopoeitic stem cells within 90 days prior to first study drug administration or loss of whole blood of more than 500 mL within 60 days prior to randomisation, or receipt of a blood transfusion within 1 year of first study drug administration. 19. Participation in another investigational clinical trial within 60 days prior to the first study drug administration. 20. Volunteers with excessive consumption of caffeine-containing products, which in the opinion of the PI, would lead to withdrawal symptoms following their discontinuation while confined to the clinic. 21. Any other condition or prior therapy that in the opinion of the PI would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements. 22. Has legal incapacity or limited legal capacity. 23. Is an employee of an investigator or Sponsor or an immediate relative of an investigator. 24. Has been institutionalized due to judicial or administrative order. 25. Presence of mental handicaps or disorders leading to inability to give informed consent.
Outcome results
None listed