A Phase 1 Randomised, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of INI-822 in Healthy Volunteers and Participants with Non-alcoholic Steatohepatitis (NASH) or Presumed NASH

Inipharm Australia Pty Ltd7 sites in 1 country104 target enrollmentSeptember 8, 2023

ConditionsNon-alcoholic Steatohepatitis

InterventionsINI-822 (A)Placebo (B)

DrugsINI-822 (A)

Overview

Phase: Phase 1
Intervention: INI-822 (A)
Conditions: Non-alcoholic Steatohepatitis
Sponsor: Inipharm Australia Pty Ltd
Enrollment: 104
Locations: 7
Primary Endpoint: Incidence of adverse events (AEs).
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

The study will consist of 4 parts: Approximately 104 participants are planned to be enroled into the study. * In Part A (SAD), approximately 48 healthy adult participants are planned to be enroled in 6 cohorts of 8 participants each (Cohorts A1 to A6, including one fasted:fed crossover cohort to assess food effect). * In Part B (MAD), approximately 24 healthy adult participants are planned to be enroled in 3 cohorts of 8 participants each (Cohorts B1 to B3). * In Part C (Pharmacodynamics), approximately 24 participants with NASH or presumed NASH are planned to be enroled in 2 cohorts of 12 participants each (Cohorts C1 to C2). * In Part D (SAD), approximately 8 healthy adult participants are planned to be enroled in 1 Cohort of 8 participants.

Registry

clinicaltrials.gov

Start Date

September 8, 2023

End Date

June 15, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Inipharm Australia Pty Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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 -
•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:
•Clinical laboratory values within normal range at Screening and Day -1 and Day 7 (Part D), as specified by the testing laboratory, unless deemed not clinically significant by the Investigator or designee. Any laboratory values \> upper limit of normal (ULN) at Screening should be discussed with the Sponsor, independent Medical Monitor (MM), or Investigator for approval prior to inclusion. Repeat testing at Screening is acceptable for out-of-range values following approval by the Investigator or designee. Inclusion of participants with laboratory values \> ULN at Day -1 and Day 7 (Part D) will be at the Investigator's discretion.
•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.

Exclusion Criteria

•A participant who meets any of the following exclusion criteria must be excluded from the study:
•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
•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):

Arms & Interventions

A (INI-822)

Participants will receive INI-822 orally once daily.

Intervention: INI-822 (A)

B (Placebo)

Participants will receive placebo orally once daily.

Intervention: Placebo (B)

Outcomes

Primary Outcomes

Incidence of adverse events (AEs).

Time Frame: Part C: Up to 9 weeks

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

Number of participants with clinical laboratory abnormalities

Time Frame: Part C: Up to 9 weeks

Secondary Outcomes

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)