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

NCT ID: NCT02316717

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-10-30

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.

Detailed Description

Subjects who provide voluntary written informed consent will be screened for eligibility. Subjects meeting all of the inclusion and none of the exclusion criteria will be eligible to participate.

Eligible subjects will be randomized at the Baseline visit to receive one of the three study treatments three times daily for a period of 24 weeks. Each subject will return to the study clinic for assessment and required study procedures on Day 7, 14 and 28 and every 4 weeks thereafter until Week 24.

Conditions

Non-alcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment Arm A

IMM-124E, 600 mg three times daily, orally plus matching placebo

Group Type: EXPERIMENTAL

IMM-124E

Intervention Type: BIOLOGICAL

IMM-124E

Treatment Arm B

IMM-124E, 1200 mg three times daily, orally

Group Type: EXPERIMENTAL

IMM-124E

Intervention Type: BIOLOGICAL

IMM-124E

Treatment Arm C

Matching placebo, three times daily, orally

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matched placebo

Interventions

IMM-124E

IMM-124E

Intervention Type: BIOLOGICAL

Placebo

Matched placebo

Intervention Type: OTHER

Eligibility Criteria

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.

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-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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immuron Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Peres

Role: STUDY_DIRECTOR

Immuron Ltd.

Locations

eStudySite

Chula Vista, California, United States

University of California San Diego

San Diego, California, United States

Quest Clinical Research

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

University of Florida Hepatology Research at CTRB

Gainesville, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Kansas City Research Institute

Kansas City, Missouri, United States

Duke Liver Centre

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Baylor St Lukes Medical Centre

Houston, Texas, United States

Brooke Army Medical Centre

Houston, Texas, United States

Pinnacle Clinical Research

Live Oak, Texas, United States

University of Virginia Medical Centre

Charlottesville, Virginia, United States

Mary Immaculate Hospital

Newport News, Virginia, United States

Bon Secours St Marys Hospital

Richmond, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Swedish Medical Centre

Seattle, Washington, United States

The Nepean Hospital

Penrith, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

The Alfred Hospital

Prahran, Victoria, Australia

Hadassah Medical Centre

Jerusalem, , Israel

Sourasky Medical Center (Ichilov)

Tel Aviv, , Israel

Countries

United States; Australia; Israel

References

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.

Reference Type: DERIVED

PMID: 36318027 (View on PubMed)

Jin L, Sun Y, Li Y, Zhang H, Yu W, Li Y, Xin Y, Alsareii SA, Wang Q, Zhang D. A synthetic peptide AWRK6 ameliorates metabolic associated fatty liver disease: involvement of lipid and glucose homeostasis. Peptides. 2021 Sep;143:170597. doi: 10.1016/j.peptides.2021.170597. Epub 2021 Jun 10.

Reference Type: DERIVED

PMID: 34118361 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IMM-124E-2001

Identifier Type: -

Identifier Source: org_study_id