Non-alcoholic Steatohepatitis (NASH) Clinical Trial
Official title:
A Phase ll, Randomized, Double-blind, Placebo-controlled Study of IMM-124E for Patients With Non-alcoholic Steatohepatitis.
Verified date | January 2020 |
Source | Immuron Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 133 |
Est. completion date | October 30, 2017 |
Est. primary completion date | October 30, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 99 Years |
Eligibility |
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-TNFa 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Box Hill Hospital | Box Hill | Victoria |
Australia | Royal Melbourne Hospital | Parkville | Victoria |
Australia | The Nepean Hospital | Penrith | New South Wales |
Australia | The Alfred Hospital | Prahran | Victoria |
Australia | Westmead Hospital | Westmead | New South Wales |
Australia | Princess Alexandra Hospital | Woolloongabba | Queensland |
Israel | Hadassah Medical Centre | Jerusalem | |
Israel | Sourasky Medical Center (Ichilov) | Tel Aviv | |
United States | University of Colorado | Aurora | Colorado |
United States | University of Virginia Medical Centre | Charlottesville | Virginia |
United States | Northwestern Memorial Hospital | Chicago | Illinois |
United States | eStudySite | Chula Vista | California |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | Duke Liver Centre | Durham | North Carolina |
United States | University of Florida Hepatology Research at CTRB | Gainesville | Florida |
United States | Baylor St Lukes Medical Centre | Houston | Texas |
United States | Brooke Army Medical Centre | Houston | Texas |
United States | Kansas City Research Institute | Kansas City | Missouri |
United States | Pinnacle Clinical Research | Live Oak | Texas |
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 | University of California San Diego | San Diego | California |
United States | Quest Clinical Research | San Francisco | California |
United States | Swedish Medical Centre | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Immuron Ltd. |
United States, Australia, Israel,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | 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 | |
Other | Regulatory T Cells (FoxP3+ CD25-CD4+) in Peripheral Blood Mononuclear Cells | Change in percent of FoxP3+ CD25-CD4+ cells in Peripheral Blood Mononuclear Cells | 0 and 24 Weeks | |
Other | Gut Microbiome From Fecal Samples | Number of participants with measurable differences in gut microbiome constituents post-treatment | 0, 4, 12 and 24 Weeks | |
Other | Serum Concentrations of LPS | Serum Concentrations of Lipopolysaccharide (LPS) (ng/mL) levels and change from Baseline | baseline to 24 Weeks | |
Other | Serum Concentrations of C-Reactive Protein (CRP) | Mean Serum Concentrations of C-Reactive Protein (CRP) at week 24 | baseline to 24 Weeks | |
Other | Serum Concentrations of CK-18 Fragments | The proportion of subjects with significant reduction of CK-18 (= 15%) between IMP 1200mg group to placebo. | baseline to 24 weeks | |
Other | Serum Concentrations of Human Adiponectin | Change from Run-in to Post-treatment in serum concentration of human Adiponectin. | 0 to 24 Weeks | |
Other | Serum Concentrations of Cytokine IL-6 | Mean Change from baseline to week 24 of serum concentration of cytokine IL-6 | 24 weeks | |
Other | Serum Concentration of Cytokine IL-12p70 | Mean change from baseline to week 24 of Serum concentration of Cytokine IL-12p70 | 24 weeks | |
Other | Serum Concentration of Interferon Gamma (IFN-?) | Mean Change from baseline to week 24 of serum concentration of IFN-gamma | 24 weeks | |
Other | Serum Concentration of Tumor Necrosis Factor Alpha (TNF-a) | Mean Change from baseline to week 24 of serum concentration of TNF-a | 24 weeks | |
Other | Serum Concentration of Glucagon-like Peptide-1 (GLP-1) | Mean Change from baseline to week 24 of serum concentration of GLP-1 | 24 weeks | |
Other | Regulatory T Cells (FoxP3+CD25-CD8+) in Peripheral Blood Mononuclear Cells | Change in percent of FoxP3+CD25-CD8+ cells in Peripheral Blood Mononuclear Cells | 0 and 24 Weeks | |
Primary | Safety Outcome Measure | Incidence of adverse events per arm/group | 24 Weeks | |
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 | baseline and 24 weeks | |
Primary | Adverse Events | Number of patients with treatment-related adverse events | 24 weeks | |
Primary | Severity of Adverse Events | Number of grade 3-5 adverse events | 24 weeks | |
Secondary | Systolic Blood Pressure | Mean change in Systolic Blood Pressure | baseline and 24 weeks | |
Secondary | Pulse Rate | Mean change in Pulse Rate from baseline to week 24 | baseline and 24 weeks | |
Secondary | Diastolic Blood Pressure | Change in Diastolic Blood Pressure | baseline and 24 weeks | |
Secondary | Respiratory Rate | Mean change in Respiratory Rate from baseline to week 24 | baseline and 24 weeks | |
Secondary | Serum Alanine Aminotransaminase (ALT) | Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24 | baseline and 24 weeks | |
Secondary | Peak Serum Concentration (Cmax) | Peak serum concentration (Cmax) of IMM-124E | 0, 4, 12 and 24 Weeks | |
Secondary | Minimum Serum Concentration (Cmin) | Minimum serum concentration (Cmin) of IMM-124E | 0, 4, 12 and 24 Weeks | |
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. | 0, 4, 12 and 24 Weeks | |
Secondary | Elimination Half Life (T1/2) | Elimination Half Life (T1/2) of IMM-124E | 0, 4, 12 and 24 Weeks | |
Secondary | Body Mass Index (BMI) | Change from Baseline of Body Mass Index (BMI) at 24 weeks | 24 Weeks | |
Secondary | Waist Circumference | Change from Baseline of Waist Circumference at 24 weeks | 24 Weeks | |
Secondary | Waist:Hip Ratio | Change from Baseline of Waist:Hip Ratio at 24 weeks | 24 Weeks | |
Secondary | Hemoglobin (HB)A1C | Change from Baseline of Hemoglobin(HB)A1C at 24 weeks | 24 Weeks | |
Secondary | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks | baseline and 24 Weeks | |
Secondary | Total Cholesterol | Change from Baseline of Total Cholesterol at 24 weeks | 24 Weeks | |
Secondary | Triglycerides | Change from Baseline of Triglycerides at 24 weeks | 24 Weeks | |
Secondary | Low Density Lipoprotein (LDL) | Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks | 24 Weeks | |
Secondary | High Density Lipoprotein (HDL) | Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks | 24 Weeks | |
Secondary | Serum Alanine Aminotransaminase (ALT) | Mean change from Baseline of serum ALT | baseline to 24 weeks | |
Secondary | Serum Aspartate Aminotransaminase (AST) | Mean change from Baseline of Serum AST | baseline to 24 Weeks | |
Secondary | Bilirubin | Mean change from Baseline of Bilirubin | baseline to 24 Weeks | |
Secondary | Albumin | Mean change from Baseline of Albumin | baseline to 24 Weeks | |
Secondary | Gamma Glutamyl Transpeptidase (GGT) | Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT) | baseline to 24 Weeks | |
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) | 24 Weeks |
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