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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02316717
First Posted: December 15, 2014
Last Update Posted: February 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Immuron Ltd.
  Purpose
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.

Condition Intervention Phase
Non-alcoholic Steatohepatitis (NASH) Biological: IMM-124E Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase ll, Randomized, Double-blind, Placebo-controlled Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis.

Resource links provided by NLM:


Further study details as provided by Immuron Ltd.:

Primary Outcome Measures:
  • Body Temperature [ Time Frame: 24 Weeks ]
    Changes in body temperature

  • Percentage Fat Content of the Liver [ Time Frame: 24 Weeks ]
    Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24

  • Adverse Events [ Time Frame: 24 weeks ]
    Number of patients with adverse events

  • Adverse Events [ Time Frame: 24 weeks ]
    Severity of adverse events

  • Respiratory Rate [ Time Frame: 24 weeks ]
    Change in Respiratory Rate

  • Pulse Rate [ Time Frame: 24 weeks ]
    Change in Pulse Rate

  • Systolic Blood Pressure [ Time Frame: 24 weeks ]
    Change in Systolic Blood Pressure

  • Diastolic Blood Pressure [ Time Frame: 24 weeks ]
    Change in Diastolic Blood Pressure

  • Hematology, Coagulation, Clinical Chemistry, Serum Lipids, Blood Glucose and Urinalysis [ Time Frame: 24 weeks ]
    Change in Clinical Laboratory tests (Hematology, Coagulation, Clinical Chemistry, Serum Lipids, Blood Glucose and Urinalysis)

  • Serum Alanine Aminotransaminase (ALT) [ Time Frame: 24 weeks ]
    Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24


Secondary Outcome Measures:
  • Peak serum concentration (Cmax) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Peak serum concentration (Cmax) of IMM-124E

  • Minimum serum concentration (Cmin) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Minimum serum concentration (Cmin) of IMM-124E

  • Area Under the Concentration Time Curve (AUC) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Area Under the Concentration Time Curve (AUC) of IMM-124E

  • Elimination Half Life (T1/2) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Elimination Half Life (T1/2) of IMM-124E

  • Body Mass Index (BMI) [ Time Frame: 24 Weeks ]
    Change from Baseline of Body Mass Index (BMI) at 24 weeks

  • Waist Circumference [ Time Frame: 24 Weeks ]
    Change from Baseline of Waist Circumference at 24 weeks

  • Waist:Hip Ratio [ Time Frame: 24 Weeks ]
    Change from Baseline of Waist:Hip Ratio at 24 weeks

  • Hemoglobin (HB)A1C [ Time Frame: 24 Weeks ]
    Change from Baseline of Hemoglobin(HB)A1C at 24 weeks

  • Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: 24 Weeks ]
    Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks

  • Total Cholesterol [ Time Frame: 24 Weeks ]
    Change from Baseline of Total Cholesterol at 24 weeks

  • Triglycerides [ Time Frame: 24 Weeks ]
    Change from Baseline of Triglycerides at 24 weeks

  • Low density lipoprotein (LDL) [ Time Frame: 24 Weeks ]
    Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks

  • High Density Lipoprotein (HDL) [ Time Frame: 24 Weeks ]
    Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks

  • Serum Alanine Aminotransaminase (ALT) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]
    Mean change from Baseline of serum ALT

  • Serum Aspartate Aminotransaminase (AST) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]
    Mean change from Baseline of Serum AST

  • Bilirubin [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]
    Mean change from Baseline of Bilirubin

  • Albumin [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]
    Mean change from Baseline of Albumin

  • Gamma Glutamyl Transpeptidase (GGT) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]
    Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)

  • Serum Alanine Aminotransaminase (ALT) [ Time Frame: 24 Weeks ]
    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)


Other Outcome Measures:
  • Inflammatory Cytokines and other markers [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Serum Concentrations of Lipopolysaccharide (LPS), C-Reactive Protein (CRP), CK-18 fragments, C-peptide, Adiponectin and Cytokines IL6, IL12, IFN gamma and TNF alpha

  • Regulatory T cells in Peripheral Blood Mononuclear Cells [ Time Frame: 0, 12 and 24 Weeks ]
    Relative levels of Regulatory T cells in Peripheral Blood Mononuclear Cells

  • Gut Microbiome from Fecal Samples [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Characterization of the gut microbiome from fecal samples by DNA extraction and Bacterial ribosomal DNA amplification and sequencing

  • Gastrointestinal LPS levels [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Gastrointestinal LPS levels from fecal samples


Estimated Enrollment: 130
Study Start Date: December 2014
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
IMM-124E, 600 mg three times daily, orally plus matching placebo
Biological: IMM-124E
IMM-124E
Experimental: Treatment Arm B
IMM-124E, 1200 mg three times daily, orally
Biological: IMM-124E
IMM-124E
Placebo Comparator: Treatment Arm C
Matching placebo, three times daily, orally
Other: Placebo
Matched 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02316717


  Show 25 Study Locations
Sponsors and Collaborators
Immuron Ltd.
Investigators
Study Director: Dan Peres Immuron Ltd.
  More Information

Responsible Party: Immuron Ltd.
ClinicalTrials.gov Identifier: NCT02316717     History of Changes
Other Study ID Numbers: IMM-124E-2001
First Submitted: November 6, 2014
First Posted: December 15, 2014
Last Update Posted: February 15, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases