Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05945537




Registration number
NCT05945537
Ethics application status
Date submitted
27/06/2023
Date registered
14/07/2023
Date last updated
15/03/2024

Titles & IDs
Public title
A Study of INI-822 in Healthy Volunteers and Participants With Non-alcoholic Steatohepatitis (NASH) or Presumed NASH
Scientific title
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
Secondary ID [1] 0 0
INI-822-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INI-822 (A)
Other interventions - Placebo (B)

Experimental: A (INI-822) - Participants will receive INI-822 orally once daily.

Placebo Comparator: B (Placebo) - Participants will receive placebo orally once daily.


Treatment: Drugs: INI-822 (A)
Different dose levels of INI-822

Other interventions: Placebo (B)
Matching placebo to INI-822
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events (AEs).
Timepoint [1] 0 0
Part A: Up to 5 Weeks
Primary outcome [2] 0 0
Incidence of adverse events (AEs).
Timepoint [2] 0 0
Part A fasted fed crossover cohort: Up to 8 weeks
Primary outcome [3] 0 0
Incidence of adverse events (AEs).
Timepoint [3] 0 0
Part B: Up to 7 weeks
Primary outcome [4] 0 0
Incidence of adverse events (AEs).
Timepoint [4] 0 0
Part C: Up to 9 weeks
Primary outcome [5] 0 0
Number of participants with clinical laboratory abnormalities
Timepoint [5] 0 0
Part A: Up to 5 Weeks
Primary outcome [6] 0 0
Number of participants with clinical laboratory abnormalities
Timepoint [6] 0 0
Part A fasted fed crossover cohort: Up to 8 weeks
Primary outcome [7] 0 0
Number of participants with clinical laboratory abnormalities
Timepoint [7] 0 0
Part B: Up to 7 weeks
Primary outcome [8] 0 0
Number of participants with clinical laboratory abnormalities
Timepoint [8] 0 0
Part C: Up to 9 weeks
Secondary outcome [1] 0 0
Plasma area under the curve (AUC) from time 0 to t (AUC0-t)
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
AUC from time 0 to infinity (AUC0-inf)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Maximum concentration (Cmax)
Timepoint [3] 0 0
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

Eligibility
Key inclusion criteria
1. 18 to 55 years of age (inclusive at the time of informed consent).

2. Clinical laboratory values within normal range at Screening and Day -1, as specified
by the testing laboratory, unless deemed not clinically significant by the
Investigator or designee.

3. Females must not be pregnant or lactating, and must use acceptable, highly effective
double contraception from Screening until 90 days after their last dose of IP or 5
half-lives, whichever is longer. 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.

4. 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 (eg, tubal occlusion,
hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or an acceptable,
highly effective contraceptive method must be used from Day -1 until study completion.
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.

5. Able and willing to attend the necessary visits to the study site.

6. Able and willing to refrain from use of tobacco and other nicotine-containing products
while at the study site.

7. 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.

8. Normal renal function (estimated glomerular filtration rate > 60 mL/min using
Cockcroft-Gault).

For Parts A and B only:

9. 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.

10. Body mass index (BMI) = 18.0 and = 30.0 kg/m2 with a maximum body weight of 120 kg.

For Part C only:

11. A diagnosis of NASH confirmed by 1 or more of the following:

1. Historical liver biopsy consistent with NASH (presence of Grade 1 steatosis,
hepatocellular ballooning, and lobular inflammation) according to the NAFLD
activity score.

2. F0-3 fibrosis according to the NASH Clinical Research Network classification
within 1 year of Screening.

3. A clinical diagnosis of NASH.

4. FibroScan-aspartate aminotransferase (FAST) score > 0.35.

12. ALT > 1.5 × ULN at 2 separate time points in the past 6 months. At least 1 time point
must be at Screening and the values must be at least 2 weeks apart.

13. Fibrosis-4 (FIB-4) score = 2.67, controlled attenuation parameter (CAP) score by
FibroScan® = 280 dB/m, and liver stiffness measurement (LSM) by FibroScan® = 14 kPa.

14. No documented weight loss > 5% in the 6 months preceding Screening.

15. If on glucagon-like peptide 1 (GLP1) agonists, sodium-glucose co-transporter 2 (SGLT2)
inhibitors, or vitamin E (dose > 400 IU/day), then should have been on a stable dose
for at least 3 months.

16. Platelet count > 150,000 and albumin > 3.5 mg/dL.

17. BMI = 18.0 and = 40.0 kg/m2.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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.

2. Blood donation or significant blood loss (> 500 mL) within 60 days prior to the first
administration of IP.

3. Plasma donation within 7 days prior to the first administration of IP.

4. Fever (body temperature > 37.7°C) or symptomatic viral or bacterial infection within 2
weeks prior to Day 1.

5. Dysphagia that would limit ability to swallow IP.

6. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its
constituents.

7. Abnormalities in physical examination at Screening and Day -1 which are deemed
clinically significant by the Investigator or designee.

8. Abnormal electrocardiogram (ECG) measurements (an average of 3 readings) at Screening
and Day -1 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).

9. 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):

1. Systolic blood pressure < 90 mmHg or > 160 mmHg OR

2. Diastolic blood pressure < 50 mmHg or > 95 mmHg OR

3. Pulse rate < 45 beats per minute (bpm) or > 100 bpm.

10. History or presence of other causes of liver disease including genetic, autoimmune,
viral, and alcoholic liver disease.

11. Cirrhosis of the liver as defined by:

1. A prior history of decompensated liver disease, including ascites, hepatic
encephalopathy, or variceal bleeding OR

2. F4 on previous liver biopsy OR

3. Historical evidence of cirrhosis on liver imaging.

12. History of hospitalisation or major surgery within 6 months prior to Screening.

13. Infections requiring parenteral antibiotics within 6 months prior to Screening.

14. Vaccination with a live vaccine within 4 weeks prior to the first administration of
IP.

15. Exposure to any significantly immune suppressing drug (including experimental
therapies as part of a clinical study) within 4 months prior to Screening or
5-half-lives, whichever is longer.

16. Positive blood screen for active infections including human immunodeficiency virus
(HIV), hepatitis B virus (HBV)or hepatitis C virus (HCV) at Screening.

17. Positive toxicology screening panel (urine test including Methamphetamine, Opiates,
Cocaine, tetrahydrocannabinol, Phencyclidine, Benzodiazepines, Barbiturates,
Methadone, tricyclic antidepressants and Amphetamine), or alcohol breath test at
Screening or Day -1.

18. History of substance abuse or dependency or history of recreational intravenous drug
use over the last 12 months (by self-declaration).

19. History of alcohol use disorder (within 9 months prior to Screening by
self-declaration) or consumption of significant amounts of alcohol (by
self-declaration), defined as > 10 standard drinks per week or > 4 standard drinks on
any single day (where 1 standard drink = 360 mL of beer, 45 mL of 40% spirit, or a 150
mL glass of wine). Participants who are unable to abstain from alcohol 72 hours prior
to Screening and Day -1 visits and until study completion are to be excluded.

20. Use of any IP or investigational medical device within 30 days for small molecules (or
5 half-lives of the IP if longer than 30 days) or 90 days for biologics prior to first
IP administration.

21. Anything that the Investigator considers would jeopardise the safety of the
participant, prevent complete participation in the study, or compromise interpretation
of study data.

22. Bariatric surgery.

23. Cardiovascular disease including heart failure with reduced left ventricular ejection
fraction, atrial fibrillation requiring anticoagulation, or any other cardiovascular
illness that, in the opinion of the Investigator, warrants exclusion from the study.

For Parts A and B only:

24. Use of (or anticipated use of) any prescription drugs (other than hormonal
contraception; oral contraceptive pills [OCPs], long-acting implantable hormones,
injectable hormones, or an intrauterine device [IUD]), any known drugs or supplements
that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes,
over-the-counter (OTC) medication, herbal remedies, supplements or vitamins within 48
hours of IP administration and during the course of the study without prior approval
of the Investigator and independent MM. Simple analgesia (paracetamol < 2 g/day) may
be permitted at the discretion of the Investigator.

25. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal,
endocrine, haematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic,
immunologic, lipid metabolism disorders, or drug hypersensitivity, as determined by
the Investigator.

26. History of or suspected malignancy. Participants with basal or squamous cell carcinoma
of the skin or carcinoma in situ that has been successfully treated could be included
at the discretion of the Investigator or designee.

For Part C only:

27. ALT = 5 × ULN.

28. Use of (or anticipated use of) any known drugs or supplements that are moderate or
strong inhibitors/inducers of CYP enzymes or any drugs that are substrates of CYP2C9
with narrow therapeutic index or any drugs that are metabolised by CYP3A4 during the
course of the study. Prescription medications for stable medical condition may be
allowable if the Investigator considers they will not interfere with the study; the
independent MM may be contacted to discuss any particular medications.

29. Participants with uncontrolled medical conditions. Participants may be included if
they have a stable medical condition (stable for at least 3 months with no change in
medication) which is not deemed by the Investigator to interfere with the study; the
independent MM may be contacted for discussion.

30. History of significant cardiovascular disease, including cardiac failure, myocardial
infarction, unstable angina, stroke or transient ischaemic attack within 6 months
prior to the first dose of IP.

31. Uncontrolled diabetes mellitus (haemoglobin A1c [HbA1c] > 8.5% at Screening).

32. Malignancy within the last 5 years; basal or squamous cell carcinoma of the skin or
carcinoma in situ that has been successfully treated could be included at the
discretion of Investigator or designee.

33. History or presence of a condition associated with significant immunosuppression.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/07/2024
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Inipharm Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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 and B and in participants with a history of NASH or presumed NASH in Part C.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05945537
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Katelyn Patterson
Address 0 0
Country 0 0
Phone 0 0
+1 209-402-1568
Fax 0 0
Email 0 0
kpatterson@inipharm.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05945537