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Trial registered on ANZCTR


Registration number
ACTRN12621001349831
Ethics application status
Approved
Date submitted
27/07/2021
Date registered
7/10/2021
Date last updated
17/09/2023
Date data sharing statement initially provided
7/10/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase I trial to study the effect of food on orally dosed IMG-7289 (Bomedemstat) in healthy adult volunteers
Scientific title
A Single Centre, Phase I, Randomised, Four-way Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of a Single Dose of Two Different Formulations of IMG-7289 (Bomedemstat) Administered Orally in Healthy Adult Volunteers
Secondary ID [1] 304676 0
IMG-7289-CTP-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute myeloid leukaemia (AML) 322948 0
Myelodysplastic syndrome (MDS) 322949 0
Condition category
Condition code
Cancer 320518 320518 0 0
Leukaemia - Acute leukaemia
Blood 321088 321088 0 0
Haematological diseases
Cancer 321089 321089 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 321237 0
Treatment: Drugs
Comparator / control treatment
Formulation 2 pharmacokinetics (PK) and safety data will be compared to Formulation 1 PK and safety when given under the same conditions (ie fed or fasted). Additionally, the PK and safety of each formulation will be compared against itself when given under fed and fasted conditions.
Control group
Active

Outcomes
Primary outcome [1] 328351 0
To evaluate the effect of food on the pharmacokinetics of two formulations of IMG-7289 when administered orally at a dose of 50 mg either after a high fat/calorie meal or after an overnight fast.
The parameters assessed for the pharmacokinetics endpoints include Maximum observed concentration (Cmax), Time to Cmax (Tmax), Area under the concentration-time curve (AUC0-tlast; AUC0-inf; AUC0-24h; AUC0-48h), Terminal elimination half-life (t1/2), Terminal elimination rate constant, Apparent total body clearance, Apparent volume of distribution
Timepoint [1] 328351 0
Day 1 on each of the four study periods (within 45 minutes before dose administration and at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 120, 168, 192, and 240 hours post-dose.
Secondary outcome [1] 398683 0
To assess the safety and tolerability of two formulations of IMG-7289 administered in a fasted and fed state
The parameters assessed to monitor this outcome include incidence, severity and relationship of adverse events, change in physical examination findings, body weight measured with a body scale in kg, body mass index (BMI), vital signs, including blood pressure measured with a sphygmomanometer, pulse rate and respiratory rate measured by visual and physical examination, body temperature measured by oral or typmpanic thermometer, electrocardiogram (ECG) used to measure electrical activity of the heart, and clinical laboratory assessments performed on blood and urine samples.
Timepoint [1] 398683 0
From time of first dose to the end of study visit (all participants will be closely monitored, asked how they are feeling, and will spend 4 nights in clinic followed by 4 follow-up visits during each of the four study periods.)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/10/2021
Date of last participant enrolment
Anticipated
Actual
5/11/2021
Date of last data collection
Anticipated
Actual
3/03/2022
Sample size
Target
16
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 20068 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 34774 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 309043 0
Commercial sector/Industry
Name [1] 309043 0
Imago BioSciences
Country [1] 309043 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Avance Clinical
Address
Level 1, 2 Ann Nelson Drive, Thebarton, SA, 5042
Country
Australia
Secondary sponsor category [1] 309980 0
None
Name [1] 309980 0
Address [1] 309980 0
Country [1] 309980 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308921 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 308921 0
Ethics committee country [1] 308921 0
Australia
Date submitted for ethics approval [1] 308921 0
22/07/2021
Approval date [1] 308921 0
01/09/2021
Ethics approval number [1] 308921 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112346 0
Dr Angela Molga
Address 112346 0
CMAX Clinical Research Pty Ltd
Level 5, 18a North Terrace, Adelaide, South Australia, 5000
Country 112346 0
Australia
Phone 112346 0
+61 4 2466 6247
Fax 112346 0
+61 8 7088 7999
Email 112346 0
Angela.Molga@sa.gov.au
Contact person for public queries
Name 112347 0
Hugh Young Rienhoff, Jr. M.D.
Address 112347 0
Imago BioSciences
329 Oyster Point Blvd., 3rd Floor
South San Francisco, CA 94080
Country 112347 0
United States of America
Phone 112347 0
+1 650 2185710
Fax 112347 0
+1 650 2166774
Email 112347 0
hugh@imagobio.com
Contact person for scientific queries
Name 112348 0
Hugh Young Rienhoff, Jr. M.D.
Address 112348 0
Imago BioSciences
329 Oyster Point Blvd., 3rd Floor
South San Francisco, CA 94080
Country 112348 0
United States of America
Phone 112348 0
+1 650 2185710
Fax 112348 0
+1 650 2166774
Email 112348 0
hugh@imagobio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.