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

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.
 
ClinicalTrials.gov Identifier: NCT02316717
Recruitment Status : Completed
First Posted : December 15, 2014
Results First Posted : February 21, 2020
Last Update Posted : February 21, 2020
Sponsor:
Information provided by (Responsible Party):
Immuron Ltd.

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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 133 participants
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.
Study Start Date : December 2014
Actual Primary Completion Date : October 30, 2017
Actual Study Completion Date : October 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Safety Outcome Measure [ Time Frame: 24 Weeks ]
    Incidence of adverse events per arm/group

  2. Percentage Fat Content of the Liver [ Time Frame: baseline and 24 weeks ]
    Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24

  3. Adverse Events [ Time Frame: 24 weeks ]
    Number of patients with treatment-related adverse events

  4. Severity of Adverse Events [ Time Frame: 24 weeks ]
    Number of grade 3-5 adverse events


Secondary Outcome Measures :
  1. Systolic Blood Pressure [ Time Frame: baseline and 24 weeks ]
    Mean change in Systolic Blood Pressure

  2. Pulse Rate [ Time Frame: baseline and 24 weeks ]
    Mean change in Pulse Rate from baseline to week 24

  3. Diastolic Blood Pressure [ Time Frame: baseline and 24 weeks ]
    Change in Diastolic Blood Pressure

  4. Respiratory Rate [ Time Frame: baseline and 24 weeks ]
    Mean change in Respiratory Rate from baseline to week 24

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

  6. Peak Serum Concentration (Cmax) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Peak serum concentration (Cmax) of IMM-124E

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

  8. 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. Time points at which data were collected: baseline pre-dose, week 4, week 12 and week 24.

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

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

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

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

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

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

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

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

  17. Low Density Lipoprotein (LDL) [ Time Frame: 24 Weeks ]
    Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks

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

  19. Serum Alanine Aminotransaminase (ALT) [ Time Frame: baseline to 24 weeks ]
    Mean change from Baseline of serum ALT

  20. Serum Aspartate Aminotransaminase (AST) [ Time Frame: baseline to 24 Weeks ]
    Mean change from Baseline of Serum AST

  21. Bilirubin [ Time Frame: baseline to 24 Weeks ]
    Mean change from Baseline of Bilirubin

  22. Albumin [ Time Frame: baseline to 24 Weeks ]
    Mean change from Baseline of Albumin

  23. Gamma Glutamyl Transpeptidase (GGT) [ Time Frame: baseline to 24 Weeks ]
    Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT)

  24. 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:
  1. Serum Concentrations of Lipopolysaccharide (LPS) [ Time Frame: 0, 4, 12 and 24 Weeks ]
    The percentage of subjects reporting at least 15% reduction in LPS, from baseline to Week 24

  2. Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells [ Time Frame: 0 and 24 Weeks ]
    Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells

  3. Gut Microbiome From Fecal Samples [ Time Frame: 0, 4, 12 and 24 Weeks ]
    Number of participants with measurable differences in gut microbiome constituents post-treatment

  4. Serum Concentrations of LPS [ Time Frame: baseline to 24 Weeks ]
    Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline

  5. Serum Concentrations of C-Reactive Protein (CRP) [ Time Frame: baseline to 24 Weeks ]
    Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24

  6. Serum Concentrations of CK-18 Fragments [ Time Frame: baseline to 24 weeks ]
    The proportion of subjects with significant reduction of CK-18 (≥ 15%) between IMP 1200mg group to placebo.

  7. Serum Concentrations of Human Adiponectin [ Time Frame: 0 to 24 Weeks ]
    Change from Run-in to Post-treatment in serum concentration of human Adiponectin.

  8. Serum Concentrations of Cytokine IL-6 [ Time Frame: 24 weeks ]
    Mean Change from baseline to week 24 of serum concentration of cytokine IL-6

  9. Serum Concentration of Cytokine IL-12p70 [ Time Frame: 24 weeks ]
    Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70

  10. Serum Concentration of Interferon Gamma (IFN-γ) [ Time Frame: 24 weeks ]
    Mean Change from baseline to week 24 of serum concentration of IFN-gamma

  11. Serum Concentration of Tumor Necrosis Factor Alpha (TNF-α) [ Time Frame: 24 weeks ]
    Mean Change from baseline to week 24 of serum concentration of TNF-α

  12. Serum Concentration of Glucagon-like Peptide-1 (GLP-1) [ Time Frame: 24 weeks ]
    Mean Change from baseline to week 24 of serum concentration of GLP-1

  13. Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells [ Time Frame: 0 and 24 Weeks ]
    Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells



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.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
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.

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


Locations
Show Show 25 study locations
Sponsors and Collaborators
Immuron Ltd.
Investigators
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Study Director: Dan Peres Immuron Ltd.
  Study Documents (Full-Text)

Documents provided by Immuron Ltd.:
Study Protocol  [PDF] May 8, 2016
Statistical Analysis Plan  [PDF] November 28, 2017

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Responsible Party: Immuron Ltd.
ClinicalTrials.gov Identifier: NCT02316717    
Other Study ID Numbers: IMM-124E-2001
First Posted: December 15, 2014    Key Record Dates
Results First Posted: February 21, 2020
Last Update Posted: February 21, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases