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

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: GM-60106; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Nucleus Network Pty Ltd
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (GM-60106); Drug: GM-60106 Dosage: Part A: 2.5, 5, 10, 20, 40, 60, or 100 mg, Part B: 5, 10, 20 mg, Part C: 10, 20 mg Dosage Form: Bovine-gelatin capsules Route of Administration: Oral	Drug: GM-60106; The participants will receive a single oral dose between 2.5 to 100 mg for Part A (SAD), Part B (MAD) once daily for 14 days, and for Part C (MAD) once daily for 28 days.
Experimental: B (Placebo); Dosage Form: Bovine-gelatin capsules Route of Administration: Oral Matching placebo has an identical formulation to the GM-60106 drug product, prepared without the active pharmaceutical ingredient	Other: Placebo; Placebo-to-match GM-60106 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess safety and tolerability of GM-60106 through incidence, nature, and severity of adverse events (AEs)	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days

Secondary Outcome Measures

Outcome Measure	Time Frame
The pharmacokinetics (PK) of GM-60106. Plasma sample will be collected for PK assessment. Parameter: maximum concentration (Cmax)	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
The pharmacokinetics (PK) of GM-60106. Plasma sample will be collected for PK assessment. Parameter: time to maximum concentration (Tmax)	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
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)	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
The pharmacokinetics (PK) of GM-60106. Urine sample will be collected for PK assessment. Parameter: Cumulative amount of drug excreted in urine (Ae)	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
The pharmacokinetics (PK) of GM-60106. Urine sample will be collected for PK assessment. Parameter: Renal clearance (CLr).	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
The pharmacodynamics (PD) of GM-60106 through liver function test (aspartate aminotransferase [AST])	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days
The pharmacodynamics (PD) of GM-60106 through liver function test (alanine aminotransferase [ALT])	Part A: Up to 43 days, Part B: Up to 49 days, Part C: Up to 63 days

Collaborators and Investigators

• Sponsor: JD Bioscience Inc.
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Principal Investigator: Sam Francis, Nucleus Network Pty Ltd -Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): February 28, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: August 24, 2022
• First Submitted That Met QC Criteria: August 24, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 21, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: JDB-106001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No