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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02316717




Registration number
NCT02316717
Ethics application status
Date submitted
6/11/2014
Date registered
15/12/2014
Date last updated
21/02/2020

Titles & IDs
Public title
A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis
Scientific title
A Phase ll, Randomized, Double-blind, Placebo-controlled Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis.
Secondary ID [1] 0 0
IMM-124E-2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic Steatohepatitis (NASH) 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
Other interventions - IMM-124E
Other interventions - Placebo

Experimental: Treatment Arm A - IMM-124E, 600 mg three times daily, orally plus matching placebo

Experimental: Treatment Arm B - IMM-124E, 1200 mg three times daily, orally

Placebo Comparator: Treatment Arm C - Matching placebo, three times daily, orally


Other interventions: IMM-124E
IMM-124E

Other interventions: Placebo
Matched placebo

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Outcome Measure - Incidence of adverse events per arm/group
Timepoint [1] 0 0
24 Weeks
Primary outcome [2] 0 0
Percentage Fat Content of the Liver - Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24
Timepoint [2] 0 0
baseline and 24 weeks
Primary outcome [3] 0 0
Adverse Events - Number of patients with treatment-related adverse events
Timepoint [3] 0 0
24 weeks
Primary outcome [4] 0 0
Severity of Adverse Events - Number of grade 3-5 adverse events
Timepoint [4] 0 0
24 weeks
Secondary outcome [1] 0 0
Systolic Blood Pressure - Mean change in Systolic Blood Pressure
Timepoint [1] 0 0
baseline and 24 weeks
Secondary outcome [2] 0 0
Pulse Rate - Mean change in Pulse Rate from baseline to week 24
Timepoint [2] 0 0
baseline and 24 weeks
Secondary outcome [3] 0 0
Diastolic Blood Pressure - Change in Diastolic Blood Pressure
Timepoint [3] 0 0
baseline and 24 weeks
Secondary outcome [4] 0 0
Respiratory Rate - Mean change in Respiratory Rate from baseline to week 24
Timepoint [4] 0 0
baseline and 24 weeks
Secondary outcome [5] 0 0
Serum Alanine Aminotransaminase (ALT) - Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24
Timepoint [5] 0 0
baseline and 24 weeks
Secondary outcome [6] 0 0
Peak Serum Concentration (Cmax) - Peak serum concentration (Cmax) of IMM-124E
Timepoint [6] 0 0
0, 4, 12 and 24 Weeks
Secondary outcome [7] 0 0
Minimum Serum Concentration (Cmin) - Minimum serum concentration (Cmin) of IMM-124E
Timepoint [7] 0 0
0, 4, 12 and 24 Weeks
Secondary outcome [8] 0 0
Area Under the Concentration Time Curve (AUC) - Area Under the Concentration Time Curve (AUC) of IMM-124E. Time points at which data were collected: baseline pre-dose, week 4, week 12 and week 24.
Timepoint [8] 0 0
0, 4, 12 and 24 Weeks
Secondary outcome [9] 0 0
Elimination Half Life (T1/2) - Elimination Half Life (T1/2) of IMM-124E
Timepoint [9] 0 0
0, 4, 12 and 24 Weeks
Secondary outcome [10] 0 0
Body Mass Index (BMI) - Change from Baseline of Body Mass Index (BMI) at 24 weeks
Timepoint [10] 0 0
24 Weeks
Secondary outcome [11] 0 0
Waist Circumference - Change from Baseline of Waist Circumference at 24 weeks
Timepoint [11] 0 0
24 Weeks
Secondary outcome [12] 0 0
Waist:Hip Ratio - Change from Baseline of Waist:Hip Ratio at 24 weeks
Timepoint [12] 0 0
24 Weeks
Secondary outcome [13] 0 0
Hemoglobin (HB)A1C - Change from Baseline of Hemoglobin(HB)A1C at 24 weeks
Timepoint [13] 0 0
24 Weeks
Secondary outcome [14] 0 0
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) - Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks
Timepoint [14] 0 0
baseline and 24 Weeks
Secondary outcome [15] 0 0
Total Cholesterol - Change from Baseline of Total Cholesterol at 24 weeks
Timepoint [15] 0 0
24 Weeks
Secondary outcome [16] 0 0
Triglycerides - Change from Baseline of Triglycerides at 24 weeks
Timepoint [16] 0 0
24 Weeks
Secondary outcome [17] 0 0
Low Density Lipoprotein (LDL) - Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks
Timepoint [17] 0 0
24 Weeks
Secondary outcome [18] 0 0
High Density Lipoprotein (HDL) - Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks
Timepoint [18] 0 0
24 Weeks
Secondary outcome [19] 0 0
Serum Alanine Aminotransaminase (ALT) - Mean change from Baseline of serum ALT
Timepoint [19] 0 0
baseline to 24 weeks
Secondary outcome [20] 0 0
Serum Aspartate Aminotransaminase (AST) - Mean change from Baseline of Serum AST
Timepoint [20] 0 0
baseline to 24 Weeks
Secondary outcome [21] 0 0
Bilirubin - Mean change from Baseline of Bilirubin
Timepoint [21] 0 0
baseline to 24 Weeks
Secondary outcome [22] 0 0
Albumin - Mean change from Baseline of Albumin
Timepoint [22] 0 0
baseline to 24 Weeks
Secondary outcome [23] 0 0
Gamma Glutamyl Transpeptidase (GGT) - Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)
Timepoint [23] 0 0
baseline to 24 Weeks
Secondary outcome [24] 0 0
Serum Alanine Aminotransaminase (ALT) - Number of patients with ALT within the normal reference range at Week 24 (defined a <19 IU/L for women and <30 IU/L for men)
Timepoint [24] 0 0
24 Weeks

Eligibility
Key inclusion criteria
1. Age = 18 years.

2. Provision of written informed consent.

3. Diagnosis of NASH, histologically proven within 12 months of Screening with

- NASH activity score (NAS) of 4 or more

- cytologic ballooning score of at least 1;

- 10% or more macrovescicular steatosis.

- Hematoxylin & Eosin (H&E) stained slides and/or paraffin block available for
independent assessment.

4. HBA1C of <9.0

5. Agree to the use of effective contraceptive measures if either male or female of child
bearing potential.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of vascular liver disease or cirrhosis;

2. Presence of liver disease with other cause (autoimmune, metabolic, medication
induced);

3. BMI <25 kg/m^2;

4. Alcohol use >30 g/day;

5. Type 1 diabetes;

6. 6. History of major bariatric surgery (not including balloon / sleeve gastrectomy);

7. Weight loss or gain of 5kg or more in the past 6 months or >10% change in bodyweight
in the past 12 months;

8. Contraindication for MRI;

9. Inadequate venous access;

10. Lactating/breastfeeding/pregnant at Screening or Baseline;

11. HIV antibody positive, hepatitis B surface antigen positive (HBsAg) or Hepatitis C
virus (HCV)-RNA positive;

12. Receiving an elemental diet or parenteral nutrition;

13. Concurrent conditions

- Inflammatory bowel disease;

- Unstable angina, myocardial infarction, transient ischemic events, or stroke
within 24 weeks of Screening;

- Ongoing infectious, ongoing multi-systemic immune-mediated and/or concurrent or
past malignant disease;

- Any other concurrent condition which, in the opinion of the investigator, could
impact adversely on the subject participating or on the interpretation of the
study data;

14. Concurrent medications including:

- anti-NASH therapy(s) taken for more than 10 continuous days in the last 3 months.
These include S-adenosyl methionine (SAM-e), betaine, milk thistle, probiotic
supplements (other than yoghurt), vitamin E and gemfibrozil.

- NB: If vitamin E or gemfibrozil are used, the dose must be stable and liver
biopsy confirming diagnosis of NASH subsequent to commencing treatment;
commencing treatment;

- Wash out for any of the anti-NASH therapies is as follows: under 10 days no
washout required, more than 10 days and up to 3 months treatment requires 6
weeks washout. Any treatment of over 3 months would require to re-biopsy to
ensure histological eligibility

- thiazolidinediones (glitazones), dipeptidyl peptidase 4 inhibitors (gliptins) or
glucagon-like peptide-1 analogs in the last 6 months. If treatment commenced and
is stable for more than 6 month prior to the determinant biopsy and the dose is
still stable at time of study entry, subjects will be eligible for recruitment.

- Allowable anti-diabetic treatment includes metformin and/or sulfonylureas
administered at constant dose for at least 2 months prior to study entry.

- Subjects treated with Insulin are eligible if clinically stable on insulin
treatment (i.e. no recurrent acute hypo-/hyperglycemic episodes diagnosed
clinically and by Glucose serum levels of <50 mg/dL and >200 mg/dL respectively)
for at least 2 months prior to study entry.

- immune modulatory agents including

- In the last 3 months:

- systemic steroids for more than 7 days.

- daily treatment with multiple non-steroidal anti-inflammatory drugs (such as
aspirin >100mg/day, ibuprofen, naproxen, meloxicam, celecoxib) for more than
1 month within 3 months prior to study entry;

- In the last 12 months:

- azathioprine, 6-mercaptopurine, methotrexate, cyclosporin, anti-TNFa
therapies (infliximab, adalimumab, etanercept) or anti-integrin therapies
(namixilab) ;

- more than 10 consecutive days oral or parenteral antibiotics within 4 weeks prior
to study entry (Note: such subjects would not be included in the stool and PBMC
analysis).

- variable dose of antilipidemic agents (3-hydroxy-3-methyl-glutaryl (HMG)-Co-A
reductase inhibitors - "statins") in the 3 months prior to study entry.

15. The following laboratory abnormalities:

- Neutrophil count =1.0 x 10^9/L

- Platelets <100 x 10^9/L

- Hemoglobin <10 g/dL

- Albumin <3.5 g/dL

- International Normalized Ratio (INR) >1.5

- Total bilirubin >1.5 x upper limit of reference range (unless Gilbert's syndrome
or extrahepatic source as denoted by increased indirect bilirubin fraction)

- Either creatinine clearance =60 mL/minute calculated by Cockroft Gault or
creatinine >1.5x upper limit of reference range.

16. Known substance abuse, including inhaled or injected drugs in the year prior to
Screening.

17. Cow milk allergy, lactose intolerance or any known or suspected hypersensitivity to
study products.

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
The Nepean Hospital - Penrith
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [6] 0 0
The Alfred Hospital - Prahran
Recruitment postcode(s) [1] 0 0
2750 - Penrith
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
3004 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Israel
State/province [11] 0 0
Jerusalem
Country [12] 0 0
Israel
State/province [12] 0 0
Tel Aviv

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Immuron Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety and preliminary efficacy of two dose levels of IMM-124E
in reducing liver fat and/or serum alanine aminotransaminase (ALT) compared with placebo.
Trial website
https://clinicaltrials.gov/show/NCT02316717
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dan Peres
Address 0 0
Immuron Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications