Clinical trial NCT05517564: 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
Official title: A Phase 1, First-in-Human, Double-blind, Placebo-controlled, Single-and Multiple-Ascending Oral Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-alcoholic Steatohepatitis
Lead sponsor: JD Bioscience Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2022-08-26
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The study consists of 3 parts:

Part A (Single Ascending Dose \[SAD\]): Approximately 56 healthy participants will be enrolled into 7 cohorts and randomised to receive either GM-60106 or matching placebo at a ratio of 6:2 (GM-60106: placebo).

Part B (Multiple Ascending Dose \[MAD\]): Approximately 24 healthy participants will be enrolled into 3 cohorts and randomised to receive either GM-60106 or matching placebo at a ratio of 6:2 (GM-60106: placebo).

Part C (Multiple Ascending Dose \[MAD\]): Approximately 16 participants will be enrolled into 2 cohorts and randomised to receive either GM-60106 or matching placebo at a ratio of 6:2 (GM-60106: placebo). Cohorts will include otherwise healthy participants who have an increased BMI and markers of NAFLD.

Part B and Part C will occur only after the Safety Monitoring Committee (SMC) has reviewed all blinded safety data as well as any available PK and PD data from MAD cohorts that have completed the assessment of doses equal to the proposed starting Part C (MAD) dose and a dose higher (including a minimum safety review interval of 10 days after dosing the sixth participant in the cohort) and recommends initiation.

The study duration for each participant in Part A (SAD) is a maximum of 36 to 43 days, including a Screening period of up to 28 days, 1 day of single dosing, and a follow-up period of 7 days for most cohorts, and food effect assessment with a total treatment and follow-up period of 15 days for one of the SAD cohorts.

The study duration for each participant in Part B (MAD) is a maximum of 49 days, including a Screening period of up to 28 days, 14 consecutive days of once daily dosing, and a follow-up period of 7 days.

The study duration for each participant in Part C (MAD) is a maximum of 63 days, including a Screening period of up to 28 days, 28 consecutive days of once daily dosing, and a follow-up period of 7 days.

Eligibility criteria: Key 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
3. Negative pregnancy test

Key exclusion criteria:

1. History or presence of clinically significant abnormalities or participants with psychosomatic disorders.
2. Positive test results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibody.
3. Dosing in other clinical studies and treatment with a study drug within 3 months prior to IP administration.
4. Females who are pregnant or breastfeeding, or of childbearing potential who are not using effective non-hormonal contraception; men of childbearing potential who are unwilling to use physical methods of contraception during the study

Primary outcomes:
measure: To assess safety and tolerability of GM-60106 through incidence, nature, and severity of adverse events (AEs)
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
Secondary outcomes:
measure: The pharmacokinetics (PK) of GM-60106. Plasma sample will be collected for PK assessment. Parameter: maximum concentration (Cmax)
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacokinetics (PK) of GM-60106. Plasma sample will be collected for PK assessment. Parameter: time to maximum concentration (Tmax)
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacokinetics (PK) of GM-60106. Plasma sample will be collected for PK assessment. Parameter: Area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last)
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacokinetics (PK) of GM-60106. Urine sample will be collected for PK assessment. Parameter: Cumulative amount of drug excreted in urine (Ae)
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacokinetics (PK) of GM-60106. Urine sample will be collected for PK assessment. Parameter: Renal clearance (CLr).
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacodynamics (PD) of GM-60106 through liver function test (aspartate aminotransferase [AST])
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
measure: The pharmacodynamics (PD) of GM-60106 through liver function test (alanine aminotransferase [ALT])
timeFrame: Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
Other outcomes:
Locations:
city: Geelong
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
affiliation: Nucleus Network Pty Ltd -Melbourne
name: Sam Francis
role: PRINCIPAL_INVESTIGATOR
References: