A Study of INI-822 in Healthy Volunteers and Participants with Non-alcoholic Steatohepatitis (NASH) or Presumed NASH

NCT05945537 | Recruiting Phase 1 DMC

• 1 other identifier: INI-822-001
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 7

Brief Summary

This Phase 1 trial will explore the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses of INI-822 in healthy volunteers in Parts A, B, and D and in participants with a history of NASH or presumed NASH in Part C.

Conditions

Non-alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (8)

• Incidence of adverse events (AEs).

  AEs will be graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Part A: Up to 5 Weeks

• Incidence of adverse events (AEs).

  AEs will be graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Part A fasted fed crossover cohort: Up to 8 weeks

• Incidence of adverse events (AEs).

  AEs will be graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Part B: Up to 7 weeks

• Incidence of adverse events (AEs).

  AEs will be graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Part C: Up to 9 weeks

• Number of participants with clinical laboratory abnormalities

  Part A: Up to 5 Weeks

• Number of participants with clinical laboratory abnormalities

  Part A fasted fed crossover cohort: Up to 8 weeks

• Number of participants with clinical laboratory abnormalities

  Part B: Up to 7 weeks

• Number of participants with clinical laboratory abnormalities

  Part C: Up to 9 weeks

Secondary Outcomes (3)

• Plasma area under the curve (AUC) from time 0 to t (AUC0-t)

  Part A: Up to 5 Weeks, Part A fasted fed crossover cohort: Up to 8 weeks, Part B: Up to 7 weeks, Part C: Up to 9 weeks

• AUC from time 0 to infinity (AUC0-inf)

  Part A: Up to 5 Weeks, Part A fasted fed crossover cohort: Up to 8 weeks, Part B: Up to 7 weeks, Part C: Up to 9 weeks

• Maximum concentration (Cmax)

  Part A: Up to 5 Weeks, Part A fasted fed crossover cohort: Up to 8 weeks, Part B: Up to 7 weeks, Part C: Up to 9 weeks

Study Arms (2)

A (INI-822)

EXPERIMENTAL

Participants will receive INI-822 orally once daily.

Drug: INI-822 (A)

B (Placebo)

PLACEBO COMPARATOR

Participants will receive placebo orally once daily.

Other: Placebo (B)

Interventions

INI-822 (A) DRUG

Different dose levels of INI-822

A (INI-822)

Placebo (B) OTHER

Matching placebo to INI-822

B (Placebo)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females must not be pregnant or lactating, and must use acceptable, highly effective double contraception (see Section 7.3.1) from Screening until 90 days after their last dose of IP or 5 half-lives, whichever is longer. Females with same-sex partners (abstinent from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Day -1. Women not of childbearing potential must be postmenopausal for ≥ 12 months (postmenopausal status is to be confirmed through testing of follicle stimulating hormone \[FSH\] levels ≥ 40 IU/L at Screening for amenorrhoeic female participants). Females must not donate ova from the first dose of IP until at least 90 days after the last dose of IP or 5 half-lives, whichever is longer.
• Males must be surgically sterile (\> 30 days since vasectomy \[documented evidence\] with no viable sperm), or, if engaged in sexual relations with a WOCBP, they must use a condom and either his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or an acceptable, highly effective contraceptive method (see Section 7.3.1) must be used from Day -1 until study completion. Males with same-sex partners (abstinent from penile-vaginal intercourse) or abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP or 5 half-lives, whichever is longer.
• Able and willing to attend the necessary visits to the study site.
• Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
• Normal renal function (estimated glomerular filtration rate \> 60 mL/min using Cockcroft-Gault).
• For Parts A and B only:
• In good general health, with no significant medical history, and no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP, at the discretion of the Investigator or designee.
• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 with a maximum body weight of 120 kg.
• to 55 years of age (inclusive at the time of informed consent).
• Able and willing to refrain from use of tobacco and other nicotine-containing products while at the study site and through the study treatment period.
• For Part C only:
• to 65 years of age (inclusive at the time of informed consent).
• \. A diagnosis of NASH confirmed by 1 or more of the following:
• Historical liver biopsy consistent with NASH (presence of Grade 1 steatosis, hepatocellular ballooning, and lobular inflammation) according to the non-alcoholic fatty liver disease (NAFLD) activity score.
• F0-3 fibrosis according to the NASH Clinical Research Network classification within 1 year of Screening.

You may not qualify if:

• An underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely for the participant to comply with the protocol or complete the study per protocol.
• Blood donation or significant blood loss (\> 500 mL) within 60 days prior to the first administration of IP.
• Plasma donation within 7 days prior to the first administration of IP.
• Fever (body temperature \> 37.7°C) or symptomatic viral or bacterial infection within 2 weeks prior to Day 1.
• Dysphagia that would limit ability to swallow IP.
• History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents. The excipients in the IP are: Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS), Microcrystalline Cellulose, Micronized Poloxamer 407 (polyoxyethylene oxide), Croscarmellose Sodium, Silicon Dioxide, Magnesium Stearate, and Hydroxypropylmethylcellulose capsules containing Titanium Oxide.
• Abnormalities in physical examination at Screening and Day -1 which are deemed clinically significant by the Investigator or designee.
• Abnormal electrocardiogram (ECG) measurements at Screening (an average of 3 readings) and Day -1 (single reading) that are considered by the Investigator or designee to be clinically significant, including corrected QT interval with Fridericia's correction (QTcF) \> 450 msec (males) or \> 470 msec (females).
• Unstable vital sign(s) or the following values seen at Screening or prior to dosing following 5 minutes of resting in the semi-supine position (an abnormal value may be repeated once, separated by at least 5 minutes, with both values documented):
• Systolic blood pressure \< 90 mmHg or \> 160 mmHg OR
• Diastolic blood pressure \< 50 mmHg or \> 95 mmHg OR
• Pulse rate \< 45 beats per minute (bpm) or \> 100 bpm.
• History or presence of other causes of liver disease including genetic, autoimmune, viral, and alcoholic liver disease.
• Cirrhosis of the liver as defined by:
• A prior history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding OR

Sponsors & Collaborators

• Inipharm Australia Pty Ltd: lead

Study Sites (7)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

RECRUITING

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

RECRUITING

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

RECRUITING

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Central Study Contacts

Katelyn Patterson

CONTACT

+1 209-402-1568; kpatterson@inipharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: July 14, 2023
• Study Start: September 8, 2023
• Primary Completion: May 15, 2025
• Study Completion: June 15, 2025
• Last Updated: February 5, 2025

Record last verified: 2025-02

Locations

AU (7)