First-in-Human Study of GM-60106 in Healthy Adults and Otherwise Healthy Adults With an Increased Body Mass Index and Markers of Non-Alcoholic Fatty Liver Disease

• Status: Enrolling by invitation
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1a/1b, randomised, double-blind, placebo-controlled single- and multiple-ascending dose study to evaluate the safety, tolerability, PK, and PD of GM-60106 in healthy adult male and female participants and otherwise healthy adults who have an increased BMI and markers of NAFLD.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: JD Bioscience Inc.
• Collaborator: Novotech (Australia) Pty Limited

Criteria

Inclusion Criteria:

1. Healthy adult males or females aged 18 to 55 years (inclusive).

2. Body weight ≥ 50 kg for males and ≥ 45 kg for females, no major changes to body weight for at least 3 months prior to Screening (weight fluctuations of 2kg or less permitted), and BMI in the range of 18.5.0 to 28.0 kg/m2 (inclusive) for the healthy participant cohorts (ie, SAD Cohorts 1 to 7 and MAD Cohorts 1 to 3); OR BMI in the range of 28.1 to 35.0 kg/m2 (inclusive) for the increased BMI yet otherwise healthy participant cohorts (ie, MAD Cohorts 4 and 5) with liver fat > 10% via MRI-PDFF as a marker of NAFLD.

3. A negative Screening serum pregnancy test and a negative urine pregnancy test during admission on Day -1 for females of childbearing potential.

4. Females of childbearing potential (non-surgically sterile or premenopausal female capable of becoming pregnant) and all males (due to potential risk of drug exposure through the ejaculate) must agree to use acceptable, highly effective birth control measures during the study and for 60 days and 120 days respectively, after the last dose of the IP.

Females of childbearing potential must not be breastfeeding, lactating or planning pregnancy during the study period. Menopause is defined as 12 months of amenorrhea in the absence of other biological causes. In addition, females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level > 40mIU/mL to confirm menopause.

Acceptable methods of birth control for females of childbearing potential include the use of a condom AND one other form of contraception including either oral contraceptive pills (OCPs), long acting implantable hormones, injectable hormones, a vaginal ring, an intrauterine device (IUD), bilateral tubal occlusion, or a vasectomised partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner. Hormonal contraceptives should begin at least 1 month prior to screening to ensure contraceptive is in full effect. Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not considered highly effective methods of birth control. Participant complete abstinence for the duration of the study and for 60 days and 120 days (females and males respectively) after the last study treatment is acceptable.

Acceptable methods of birth control for males include the use of a condom AND one other form of contraception including either surgical sterilisation (> 30 days since vasectomy with no viable sperm), complete abstinence for the duration of the study and for 120 days after the last study treatment, or the use of an effective contraceptive for the female partner that includes OCPs, long acting implantable hormones, injectable hormones, a vaginal ring, an IUD, or a bilateral tubal occlusion. Males must not donate sperm for 120 days after the final dose. Participants with same-sex partners (abstinence from penile-vaginal intercourse) are eligible to participate without the use of contraception when this is their preferred and usual lifestyle.

5. No clinically significant findings in vital signs, physical examination, laboratory tests, or ECG.

6. FibroScan® (VTCE) result > 7 kPa and < 13 kPa for the increased BMI and markers of NAFLD cohorts.

7. Documented evidence of a completed course of a licensed COVID-19 vaccination.

8. Willing to consume an IP containing animal excipient (bovine-gelatin capsule)

9. Participants understand and comply with the study procedures, voluntarily participate, and sign an Informed Consent Form.

Exclusion Criteria:

1. History or presence of clinically significant abnormalities, eg, significant abnormality or disease of endocrine, gastrointestinal, cardiovascular, haematologic, hepatic, immunologic, renal, respiratory, genitourinary, or major neurological (including stroke and chronic epilepsy) or participants with psychosomatic disorders. Participants who have a history of childhood asthma that is fully resolved with no recurrences may be enrolled in this study.

2. History of clinically significant ECG abnormalities or family history of long QT syndrome (grandparents, parents, and siblings), or any of the following:

1. Confirmation of QTcF ≥ 450 ms by repeated measurements in men, QTcF ≥ 470 ms in females.

2. Confirmation of QRS duration > 120 ms by repeated measurements.

3. Confirmation of PR interval > 200 ms by repeated measurements.

4. Findings that make QTc measurement difficult or QTc data difficult to interpret.

5. History of other risk factors for Torsades de Pointes tachycardia (eg, heart failure, hypokalaemia, family history of long QT syndrome).

6. Presence of uncorrected hypokalaemia or hypomagnesaemia.

3. History of allergy to the IP or its excipient components, or a history of clinically significant severe allergy (eg, food, drug, latex allergy), or a history of atopic allergic disease (asthma, urticaria, eczematous dermatitis).

4. History of dysphagia or any gastrointestinal disorder affecting drug absorption at Screening, including the history of frequent nausea or vomiting of any aetiology, history of irregular gastrointestinal motility such as habitual diarrhoea, constipation or pre-irritable bowel syndrome, or history of major gastrointestinal surgery (eg, gastrectomy, gastrointestinal anastomosis, bowel resection, gastric bypass, gastric division, gastric banding, or cholecystectomy). Participants with a history of appendectomy may be enrolled in this study.

5. History of pancreatic injury or pancreatitis at Screening or significantly elevated blood amylase (> 1.5 × the upper limit of normal [ULN]).

6. History of urinary tract obstruction or presence of urinary voiding difficulties at Screening.

7. History of cancer (malignancy).

8. Positive test results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or syphilis antibody.

Positive COVID-19 Rapid Antigen Test (RAT) or PCR test if the site requires COVID-19 testing at visitation.

9. History of significant drug abuse within 12 months prior to Screening or positive urine drug test at Screening or Day -1.

10. Regular alcohol consumption within 3 months prior to Screening, consuming more than 2 alcoholic drinks per day or 14 alcoholic drinks per week (1 drink is approximately equal to: beer 354 mL/12 oz, wine 118 mL/4 oz, or distilled spirits 29.5 mL/1 oz), or evidence of alcohol abuse and excessive consumption as evidenced by alcohol breath test at Screening and Day -1 (participants consuming 3 alcoholic drinks per day may be enrolled at the discretion of the Investigator). Participants who are not willing to refrain from alcohol consumption from 48 hours prior to CRU admission on Day -1 to EOS will be excluded.

11. History of smoking or vaping the equivalent of > 2 cigarettes per day within 3 months prior to Screening, or a positive urine cotinine test at Screening or Day -1. Participants who are not willing to refrain from smoking or vaping from 48 hours prior to CRU admission on Day -1 to EOS will be excluded.

12. Excessive daily intake of coffee, tea, cola, energy drinks, or other caffeinated beverages within 3 months prior to Screening, with excess defined as more than 4 servings (1 serving is approximately equal to 120 mg of caffeine).

13. Major surgery or loss of blood over 400 mL within 3 months prior to IP administration. Blood donation within 30 days and plasma donation within 7 days prior to IP administration.

14. Dosing in other clinical studies and treatment with a study drug within 3 months prior to IP administration.

15. Implanted battery-operated devices such as pacemakers or defibrillators.

16. Use of any prescription, over-the-counter (OTC), health product, herbal or proprietary Chinese medicine or Omega-3 supplementation within 4 weeks before administration (or less than 5 half-lives of the drug from the start of the study) but permitting the use of hormonal contraception or occasional paracetamol at doses up to 2 g/day. Other exclusions are:

1. Use of hormone replacement therapy (HRT);

2. Use of St John's Wort within 14 days prior to IP administration (or less than 5 half-lives of the drug from the start of the study);

3. Consumption of grapefruit or products containing grapefruit within 5 days prior to IP administration; and

4. Vaccinations within 2 weeks prior to IP administration.

5. Blood pressure and cholesterol medications permitted for the increased BMI yet otherwise healthy participant cohorts (ie, MAD Cohorts 4 and 5) if the health condition has been well managed, on a stage dose, for at least 3 months.

17. Females who are pregnant or breastfeeding, or of childbearing potential who are not using effective non-hormonal contraception (IUD, barrier method, or surgical sterilisation, etc.) or are unwilling to continue using these methods during the study until 90 days after discontinuation; men of childbearing potential who are unwilling to use physical methods of contraception during the study until 120 days after discontinuation.

18. At Screening or Day -1, hemodynamically unstable with systolic blood pressure > 140 mmHg or < 90 mmHg, and/or diastolic blood pressure > 90 mmHg or < 50 mmHg after 5 minutes in the supine position.

19. At Screening or Day -1, heart rate < 45 or > 100 beats/minute after 5 minutes in the supine position.

20. At Screening or Day -1, glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 estimated according to the Chronic Kidney Disease Epidemic (CKD-EPI) formula (see Annex 1 for calculation formula).

21. At Screening or Day -1, the liver function tests show any measure of AST, ALT, ALP, or total bilirubin is > ULN in healthy participant cohorts; OR liver function tests show AST < 40 U/L, ALT < 40 U/L, ALP is > 1.5 × ULN, albumin > 3.8 g/dL, and total bilirubin is < 0.4 mg/dL in the otherwise healthy with increased BMI and markers of NAFLD cohorts. Testing can be repeated up to 2 times at Screening and levels outside this range demonstrating non-clinically significant abnormalities may be considered for inclusion at the discretion of the Investigator.

22. At Screening or Day -1, platelet count > 150,000 and international normalised ratio (INR) > 1.3 in the otherwise healthy with increased BMI and markers of NAFLD cohorts. Testing can be repeated up to 2 times at Screening (particularly if individuals have an INR of > 1.4) and levels outside this range demonstrating non-clinically significant abnormalities may be considered for inclusion at the discretion of the Investigator.

23. At Screening or Day -1, fasting triglycerides > 2.3 mmol/L. Testing can be repeated up to 2 times at Screening and levels outside this range demonstrating non-clinically significant abnormalities may be considered for inclusion at the discretion of the Investigator.

24. At Screening or Day -1, fasting glucose > 5.6 mmol/L in the healthy participant cohorts; OR fasting glucose > 6.1 mmol/L or glycosylated haemoglobin (HbA1c) ≥ 6.5% in the increased BMI and markers of NAFLD cohorts. Testing can be repeated up to 2 times at Screening and levels outside this range demonstrating non-clinically significant abnormalities may be considered for inclusion at the discretion of the Investigator. Participants unable to tolerate blood sample collection.

25. Participants who the Investigator deems to be unsuitable for participation in the study.