A Phase ll Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis

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 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 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 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.
• Kno