A Phase ll Study of IMM-124E for Patients With Non-alcoho... | NCT02316717

NCT02316717

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Arm A	Experimental	IMM-124E, 600 mg three times daily, orally plus matching placebo	Biological: IMM-124E
Treatment Arm B	Experimental	IMM-124E, 1200 mg three times daily, orally	Biological: IMM-124E
Treatment Arm C	Placebo Comparator	Matching placebo, three times daily, orally	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
IMM-124E	Biological	IMM-124E	Treatment Arm A Treatment Arm B

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety Outcome Measure	Incidence of adverse events per arm/group	24 Weeks
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	baseline and 24 weeks
Adverse Events	Number of patients with treatment-related adverse events	24 weeks
Severity of Adverse Events	Number of grade 3-5 adverse events	24 weeks

Measure	Description	Time Frame
Systolic Blood Pressure	Mean change in Systolic Blood Pressure	baseline and 24 weeks
Pulse Rate	Mean change in Pulse Rate from baseline to week 24

Other Outcomes

Measure	Description	Time Frame
Serum Concentrations of Lipopolysaccharide (LPS)	The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24	0, 4, 12 and 24 Weeks
Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years.
Provision of written informed consent.
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.
HBA1C of <9.0
Agree to the use of effective contraceptive measures if either male or female of child bearing potential.

Exclusion Criteria:

Presence of vascular liver disease or cirrhosis;
Presence of liver disease with other cause (autoimmune, metabolic, medication induced);
BMI <25 kg/m^2;
Alcohol use >30 g/day;
Type 1 diabetes;
6. History of major bariatric surgery (not including balloon / sleeve gastrectomy);
Weight loss or gain of 5kg or more in the past 6 months or >10% change in bodyweight in the past 12 months;
Contraindication for MRI;
Inadequate venous access;
Lactating/breastfeeding/pregnant at Screening or Baseline;
HIV antibody positive, hepatitis B surface antigen positive (HBsAg) or Hepatitis C virus (HCV)-RNA positive;
Receiving an elemental diet or parenteral nutrition;
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;
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-TNFα 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.
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.
Known substance abuse, including inhaled or injected drugs in the year prior to Screening.
Cow milk allergy, lactose intolerance or any known or suspected hypersensitivity to study products.

Contacts/Locations Module

Name	Affiliation	Role
Dan Peres	Immuron Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
eStudySite		Chula Vista	California	91911	United States
University of California San Diego

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36318027	Derived	Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.
34118361	Derived

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
FG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 8, 2016	Nov 13, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
BG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
BG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00051.4± 11.9 BG00150.2± 13.7 BG00250.2± 11.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00023 BG00127 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00034 BG00132 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00033.97± 5.439 BG00134.12± 5.802 BG002

HbA1c

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG0006.14± 0.765 BG0016.16± 0.999 BG002

Hepatic Fat

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00019.64± 9.237 BG00119.11± 8.166 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Safety Outcome Measure

Incidence of adverse events per arm/group

Number of treatment emerged AEs per arm/group

Posted

Number

AEs

24 Weeks

ID	Title	Description
OG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment
OG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment
OG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment

Units	Counts
Participants	OG00043 OG00146 OG00244

Title

Denominators

Categories

Title	Measurements
	OG000185 OG001207 OG002155

Primary

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

The analysis population includes subjects with both baseline MRI and week 24 MRI.

Posted

Mean

Standard Deviation

percentage of hepatic fat fraction

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Primary

Adverse Events

Number of patients with treatment-related adverse events

Number of patients with any treatment-related AE

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment
OG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment
OG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment

Units	Counts
Participants	OG000

Primary

Severity of Adverse Events

Number of grade 3-5 adverse events

Number of grade 3-5 AEs

Posted

Number

events

24 weeks

ID	Title	Description
OG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment
OG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment
OG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment

Units	Counts
Participants	OG000

Secondary

Systolic Blood Pressure

Mean change in Systolic Blood Pressure

The analysis population include subjects with data of both baseline and week 24

Posted

Mean

Standard Deviation

mmHg

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Pulse Rate

Mean change in Pulse Rate from baseline to week 24

The analysis population include subjects with Pulse Rate data of both baseline and week 24

Posted

Mean

Standard Deviation

beats/minute

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Diastolic Blood Pressure

Change in Diastolic Blood Pressure

The analysis population include subjects with data of both baseline and week 24

Posted

Mean

Standard Deviation

mmHg

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Respiratory Rate

Mean change in Respiratory Rate from baseline to week 24

The analysis population includes subjects with both respiratory rate data at baseline and week 24

Posted

Mean

Standard Deviation

breaths/minute

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Serum Alanine Aminotransaminase (ALT)

Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24

Posted

Mean

Standard Deviation

IU/L

baseline and 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Peak Serum Concentration (Cmax)

Peak serum concentration (Cmax) of IMM-124E

The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.

Posted

Mean

Standard Deviation

ng/mL

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Secondary

Minimum Serum Concentration (Cmin)

Minimum serum concentration (Cmin) of IMM-124E

The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.

Posted

Mean

Standard Deviation

ng/mL

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Secondary

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.

The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.

Posted

Mean

Standard Deviation

ng/mL

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Secondary

Elimination Half Life (T1/2)

Elimination Half Life (T1/2) of IMM-124E

The investigational product is orally active and not systemically absorbed into the blood stream. This analysis purpose was to confirm this claim and show there is no absorption to blood stream.

Posted

Mean

Standard Deviation

seconds

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Secondary

Body Mass Index (BMI)

Change from Baseline of Body Mass Index (BMI) at 24 weeks

Posted

Mean

Standard Deviation

kg/m^2

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Waist Circumference

Change from Baseline of Waist Circumference at 24 weeks

Posted

Mean

Standard Deviation

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Waist:Hip Ratio

Change from Baseline of Waist:Hip Ratio at 24 weeks

Posted

Mean

Standard Deviation

ratio

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Hemoglobin (HB)A1C

Change from Baseline of Hemoglobin(HB)A1C at 24 weeks

Posted

Mean

Standard Deviation

percentage

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks

HOMA-IR is calculated according to the formula: fasting insulin (mU/mL) x fasting glucose (mmol/L)/22.5

Posted

Mean

Standard Deviation

no unit

baseline and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Secondary

Total Cholesterol

Change from Baseline of Total Cholesterol at 24 weeks

Posted

Mean

Standard Deviation

mmol/l

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Triglycerides

Change from Baseline of Triglycerides at 24 weeks

Posted

Mean

Standard Deviation

mmol/l

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Low Density Lipoprotein (LDL)

Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks

Posted

Mean

Standard Deviation

mmol/l

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

High Density Lipoprotein (HDL)

Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks

Posted

Mean

Standard Deviation

mmol/l

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Serum Alanine Aminotransaminase (ALT)

Mean change from Baseline of serum ALT

assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

IU/L

baseline to 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Serum Aspartate Aminotransaminase (AST)

Mean change from Baseline of Serum AST

assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

IU/L

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Bilirubin

Mean change from Baseline of Bilirubin

assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

umol/l

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Albumin

Mean change from Baseline of Albumin

assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

g/dL

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

Gamma Glutamyl Transpeptidase (GGT)

Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)

assessed at 0, 4, 8, 12, 16, 20 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

U/L

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Secondary

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)

Posted

Count of Participants

Participants

24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentrations of Lipopolysaccharide (LPS)

The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24

excluding subjects with < 250 LPS at baseline (comparing 1200mg IMP group to Placebo group). PP population, excluding outliers sites. this Outcome Measure was pre-specified to be assessed in the 1200mg and Placebo Arms/Groups *only*

Posted

Count of Participants

Participants

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Other Pre-specified

Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells

Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells

Sub group population with PBMC FACS data, selected sites only.

Posted

Mean

Standard Deviation

percentage of cells

0 and 24 Weeks

ID	Title	Description
OG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment
OG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment
OG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment

Units	Counts
Participants	OG000

Other Pre-specified

Gut Microbiome From Fecal Samples

Number of participants with measurable differences in gut microbiome constituents post-treatment

Posted

Count of Participants

Participants

0, 4, 12 and 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentrations of LPS

Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline

assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

ng/mL

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentrations of C-Reactive Protein (CRP)

Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24

assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

mg/L

baseline to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentrations of CK-18 Fragments

The proportion of subjects with significant reduction of CK-18 (≥ 15%) between IMP 1200mg group to placebo.

FAS population, excluding outlier sites. this Outcome Measure was pre-specified to be assessed in the 1200mg and Placebo Arms/Groups *only*

Posted

Count of Participants

Participants

baseline to 24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Other Pre-specified

Serum Concentrations of Human Adiponectin

Change from Run-in to Post-treatment in serum concentration of human Adiponectin.

ITT population. Run-in = mean of screening and baseline values. assessed at 0, 4, 12 and 24 Weeks, change from baseline to week 24 reported

Posted

Mean

Standard Deviation

pg/mL

0 to 24 Weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants

Other Pre-specified

Serum Concentrations of Cytokine IL-6

Mean Change from baseline to week 24 of serum concentration of cytokine IL-6

ITT population

Posted

Mean

Standard Deviation

pg/mL

24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentration of Cytokine IL-12p70

Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70

ITT population

Posted

Mean

Standard Deviation

pg/mL

24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentration of Interferon Gamma (IFN-γ)

Mean Change from baseline to week 24 of serum concentration of IFN-gamma

ITT population

Posted

Mean

Standard Deviation

pg/mL

24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α)

Mean Change from baseline to week 24 of serum concentration of TNF-α

ITT population

Posted

Mean

Standard Deviation

pg/mL

24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Serum Concentration of Glucagon-like Peptide-1 (GLP-1)

Mean Change from baseline to week 24 of serum concentration of GLP-1

ITT population

Posted

Mean

Standard Deviation

24 weeks

ID	Title	Description
OG000	Treatment Arm A	IMM-124E, 600 mg three times daily, orally plus matching placebo IMM-124E: IMM-124E
OG001	Treatment Arm B	IMM-124E, 1200 mg three times daily, orally IMM-124E: IMM-124E
OG002	Treatment Arm C	Matching placebo, three times daily, orally Placebo: Matched placebo

Units	Counts
Participants	OG000

Other Pre-specified

Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells

Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells

Sub group population with PBMC FACS data, selected sites only.

Posted

Mean

Standard Deviation

percentage of cells

0 and 24 Weeks

ID	Title	Description
OG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment
OG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment
OG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IMM-124E, 600 mg	IMM-124E, 600 mg three times daily, orally plus matching placebo 24 weeks of treatment	0	43	1	43	39	43
EG001	IMM-124E, 1200 mg	IMM-124E, 1200 mg three times daily, orally 24 weeks of treatment	0	46	2	46	41	46
EG002	Matching Placebo	Matching placebo, three times daily, orally 24 weeks of treatment	1	44	3	44	38	44

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chest Pain	General disorders	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0011 events1 affected46 at risk EG0020 events0 affected44 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0010 events0 affected46 at risk EG0021 events1 affected44 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0010 events0 affected46 at risk EG0021 events1 affected44 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment		EG0001 events1 affected43 at risk EG0010 events0 affected46 at risk EG0020 events0 affected44 at risk
Anxiety	Product Issues	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0011 events1 affected46 at risk EG0020 events0 affected44 at risk
Hospitalisation	Surgical and medical procedures	MedDRA 20.1	Systematic Assessment	Psychiatric hospitalisation	EG0000 events0 affected43 at risk EG0010 events0 affected46 at risk EG0021 events1 affected44 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG00010 events8 affected43 at risk EG00116 events15 affected46 at risk EG00216 events11 affected44 at risk
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment		EG00010 events8 affected43 at risk EG0013 events3 affected46 at risk EG0023 events3 affected44 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG00016 events11 affected43 at risk EG00117 events8 affected46 at risk EG00210 events8 affected44 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG0004 events4 affected43 at risk EG0016 events6 affected46 at risk EG0022 events2 affected44 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0014 events3 affected46 at risk EG0020 events0 affected44 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	lower and/or upper	EG00011 events8 affected43 at risk EG0018 events6 affected46 at risk EG00210 events9 affected44 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG0006 events4 affected43 at risk EG0018 events7 affected46 at risk EG0024 events4 affected44 at risk
Flatulence	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG0005 events5 affected43 at risk EG0016 events5 affected46 at risk EG0025 events4 affected44 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment		EG0004 events4 affected43 at risk EG0014 events3 affected46 at risk EG0027 events5 affected44 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0013 events3 affected46 at risk EG0022 events2 affected44 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0002 events2 affected43 at risk EG0013 events3 affected46 at risk EG0025 events2 affected44 at risk
Sinusitis	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0003 events2 affected43 at risk EG0014 events3 affected46 at risk EG0022 events2 affected44 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0002 events2 affected43 at risk EG0016 events5 affected46 at risk EG0025 events5 affected44 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0010 events0 affected46 at risk EG0024 events3 affected44 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0013 events3 affected46 at risk EG0022 events2 affected44 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment		EG0005 events5 affected43 at risk EG0015 events5 affected46 at risk EG0023 events3 affected44 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment		EG0000 events0 affected43 at risk EG0015 events4 affected46 at risk EG0020 events0 affected44 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment		EG0001 events1 affected43 at risk EG0017 events5 affected46 at risk EG0022 events1 affected44 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment		EG0003 events3 affected43 at risk EG0010 events0 affected46 at risk EG0020 events0 affected44 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment		EG0002 events2 affected43 at risk EG0016 events6 affected46 at risk EG0022 events2 affected44 at risk

ID	Term
D065626	Non-alcoholic Fatty Liver Disease

OG00033
OG00139
OG00240

OG0000
OG00128
OG00229

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases