Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001710819
Ethics application status
Approved
Date submitted
19/10/2021
Date registered
13/12/2021
Date last updated
6/07/2022
Date data sharing statement initially provided
13/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2 clinical study to evaluate the efficacy, safety and tolerability of TransT3-60 vs placebo (a powder administered sublingually) in participants with Non-Alcoholic SteatoHepatitis (NASH)
Scientific title
A Randomised, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Sublingual TransT3-60 in the Treatment of Non-Alcoholic SteatoHepatitis (NASH)
Secondary ID [1] 305592 0
IVB001-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver- Non-Alcoholic SteatoHepatitis (NASH) 324016 0
Condition category
Condition code
Inflammatory and Immune System 321522 321522 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 321523 321523 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
60mg tocotrienol (TransT3-60) powder, self-administered sublingually three times daily for 24 weeks.

Supervised administration: The participant will self-administer their first dose on site under the supervision of a qualified study staff member during their first dosing appointment.
Prior to this first dose, participants will be instructed on how to self-administer the powder. This process includes the staff member going through an instruction sheet on how to self-administer the powder, a copy of which will be provided to the participant to take home. The staff member will provide the opportunity for the participant to ask any questions about the administration process if they are unsure.

After the first dose, a self-report diary will be provided to the participant to record all subsequent dosing details, as well as any adverse reactions and concomitant medications they may have while on study. The staff member will instruct the participant on how to fill out the diary, and the participant will be able to ask any questions if needed. The diary will include contact details in the event the participant has any questions about self-administration while at home. Study staff will also confirm during subsequent clinic visits that the participant is adhering to the administration requirements.
Intervention code [1] 321989 0
Treatment: Drugs
Comparator / control treatment
60mg Placebo powder, self-administered sublingually three times daily for 24 weeks. Ingredients- mannitol, dextrose anhydrous, pregelatinised starch, silicone colloidal dioxide, maltodextrin, magnesium stearate, talcum, dibasic calcium phosphate, peppermint flavour, propylene glycol, sucralose.
Control group
Placebo

Outcomes
Primary outcome [1] 329288 0
Safety measured by incidence of treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) using the following parameters:

Clinical laboratory tests measured using blood and urine samples,
Vital sign measurements (blood pressure, pulse, respiratory rate) using a sphygmomanometer. Body temperature will be measured using a tympanic thermometer or oral thermometer.
Participant Diary entries for the recording of any changes in health and medications (using a physical paper diary).
Timepoint [1] 329288 0
AEs will be assessed from Screening/Baseline through to end of study Day 196 via the following safety parameters:

Clinical laboratory tests taken at:
Screening/Baseline visit, pre commencement of intervention at day 1, post commencement of intervention at days 28, 56, 84, 112, 140, 168 and 196.

Vital sign measurements (blood pressure, pulse, respiratory rate, body temperature) taken at:
Screening/Baseline visit, pre commencement of intervention at day 1, post commencement of intervention at days 28, 56, 84, 112, 140, 168 and 196.

Participant Diary entries for the recording of any changes in health and medications from:
Post commencement of intervention at days 1, 28, 56, 84, 112, 140, 168 and 196.
Primary outcome [2] 329289 0
Mean change from Screening/Baseline to Week 24 (Day 168) of hepatic steatosis using Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF).
Timepoint [2] 329289 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [1] 402032 0
Change from Screening/Baseline in liver elasticity measured by Fibroscan using Controlled Attenuated Parameter (CAP).
Timepoint [1] 402032 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [2] 402033 0
Assessing changes from Screening/Baseline in liver fibrosis using Fibrosis-4 (FIB-4) scores.
Timepoint [2] 402033 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [3] 403872 0
Assessing changes from Screening/Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) assessed from blood sample results.
Timepoint [3] 403872 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [4] 403873 0
Assessing changes from Screening/Baseline in Liver Function Tests (LFTs) assessed using blood samples.
Timepoint [4] 403873 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [5] 403874 0
Assessing changes from Screening/Baseline in body weight measurements using standing scales.
Timepoint [5] 403874 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.
Secondary outcome [6] 403875 0
Assessing changes from Screening/Baseline in waist circumference using a standard measuring tape.
Timepoint [6] 403875 0
Screening/Baseline, post commencement of intervention at Days 84 and 168.

Eligibility
Key inclusion criteria
1. Age greater than 18 years.
2. Patients will be selected by investigators as likely to have NASH but not cirrhosis, based on the patient’s history, physical examination, imaging and laboratory tests or incidental recent liver biopsy.
3. MRI-PDFF hepatic fat fraction should be >8%.
4. Fibroscan score should indicate NASH and not cirrhosis.
5. Participant must read and understand the informed consent form and must have signed it prior to any study-related procedures being performed.
6. Willingness and ability to comply with all scheduled study visits and study procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Chronic hepatitis B and C. Patients who are HCV PCR negative and have been negative for at least 12 months may be included. Patients with HBV on antiviral therapy with a HBV DNA <20 IU/mL for at least 6 months may be included.
2. HIV antibody positive.
3. Concomitant liver disease such as autoimmune hepatitis, primary biliary cirrhosis and Wilson’s disease.
4. Decompensated advanced liver disease and cirrhosis.
5. Treatment with medications known to cause fatty liver such as methotrexate, atypical neuroleptics and tamoxifen.
6. Uncontrolled hypo or hyperthyroidism.
7. Uncontrolled diabetes, HBA1c >9.
8. Active coronary artery disease defined as persisting angina.
9. Chronic kidney disease with an eGFR<60mL/min.
10. Platelet count<100,000/mm3, INR>1.3, ALT>5XULN.
11. Alcohol use >20g/day or substance abuse in the last 12 months.
12. Treatment with insulin sensitisers such as glitazones.
13. Treatment with silymarin (milk thistle).
14. Treatment with vitamin E (tocopherol) in the 4 weeks prior to study entry and for the duration of study participation.
15. Patients who are unable or unwilling to comply with the protocol requirements.
16. Women who are pregnant or lactating at the time of Randomisation.
17. Participation in any investigational study within 8 weeks of screening visit.
18. Participant has any other medical condition that, in the opinion of the investigator and/or medical monitor, would make the participant unsuitable for the study.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/01/2022
Actual
5/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 309957 0
Commercial sector/Industry
Name [1] 309957 0
Invictus Ops Pty Ltd
Country [1] 309957 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Invictus Ops Pty Ltd
Address
Level 45, MC Centre
19 Martin Place
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 311000 0
None
Name [1] 311000 0
Address [1] 311000 0
Country [1] 311000 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309672 0
Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 309672 0
Office for Research, The Royal Melbourne Hospital, Level 2 South West, 300 Grattan Street Parkville Victoria 3050
Ethics committee country [1] 309672 0
Australia
Date submitted for ethics approval [1] 309672 0
Approval date [1] 309672 0
30/09/2021
Ethics approval number [1] 309672 0

Summary
Brief summary
Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by a build-up of fat in the liver. This build-up causes inflammation and damage, known as NASH, leading to scarring of the liver and developing the life-threatening condition of cirrhosis. There are no medicines currently approved for the treatment of NASH. Current treatments include dietary changes, weight loss, increased exercise and treatment of associated dyslipidaemia and metabolic syndrome.

Recent studies suggest that lifestyle changes (nutritional counselling and exercise) with or without 100mg per day of a mixed tocotrienol product for 3 months showed a decrease in liver stiffness. 79% of those who improved were from the tocotrienol group and 21% from the lifestyle only group.

This study will compare treatment with the tocotrienol, TransT3-60, a sublingual powder, to matching placebo, to compare the effects on liver structure measured by ultrasound and magnetic resonance imaging. Safety assessments will be conducted at baseline and 4 weekly intervals.

A total of 80 participants will be randomly allocated (1:1) to either the tocotrienol treatment (TransT3-60) or to the placebo group for 24 weeks.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114986 0
Dr Siddharth Sood
Address 114986 0
The Royal Melbourne Hospital, City Campus, 300 Grattan Street, Parkville Victoria 3050
Country 114986 0
Australia
Phone 114986 0
+61 3 9342 7470
Fax 114986 0
Email 114986 0
siddharth.sood@mh.org.au
Contact person for public queries
Name 114987 0
Dr David Kingston
Address 114987 0
Invictus Ops Pty Ltd
Level 45, MC Centre 19 Martin Place Sydney NSW 2000
Country 114987 0
Australia
Phone 114987 0
+61 408 444 814
Fax 114987 0
Email 114987 0
david.kingston@invictusbiopharma.com
Contact person for scientific queries
Name 114988 0
Dr David Kingston
Address 114988 0
Invictus Ops Pty Ltd
Level 45, MC Centre 19 Martin Place Sydney NSW 2000
Country 114988 0
Australia
Phone 114988 0
+61 408 444 814
Fax 114988 0
Email 114988 0
david.kingston@invictusbiopharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.