Clinical Trial to Evaluate Efficacy of GR-MD-02 for Treatment of Liver Fibrosis in Patients With NASH With Advanced Fibrosis

Study Overview
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Brief Summary
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A Randomized, Controlled, Double-blind, Parallel Group, Single Center Phase 2 Clinical Trial to Evaluate Multiple Non-Invasive Liver Fibrosis Imaging Methods in the Assessment of the Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis in Patients with NASH with Advanced Fibrosis

Detailed Description
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The primary objective is to determine the difference between placebo and GR-MD-02 treatment in the baseline adjusted mean change in liver fibrosis as measured by corrected T1 (cT1) mapping as determined from LiverMultiScan (LMS), a multi-parametric MRI protocol. Secondary objectives include evaluating differences between subjects treated with GR-MD-02 versus placebo in: The baseline-adjusted change in liver stiffness as measured by MR-elastography The baseline-adjusted change in liver stiffness as measured by FibroScan® scores. An exploratory objective will be to evaluate the correlation of the three diagnostic modalities of LiverMultiScan, MR-Elastography, and FibroScan®.

Official Title
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Phase 2 Study to Evaluate Non-Invasive Imaging Methods in Efficacy Assessment of GR-MD-02 for the Treatment of Liver Fibrosis in Patients With NASH With Advanced Fibrosis

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: GR-MD-02
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have liver biopsy demonstrating NASH with Brunt Stage 3 fibrosis within 12 months of randomization. The subject is ≥ 18 years of age and ≤ 75 years old at the time of screening The subject is willing and able to provide written informed consent The subject is not pregnant and must have a negative pregnancy test prior to start of the study. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential. Fertile men and women participating in heterosexual relations must agree to use effective means of contraception throughout their participation in this study and for 90 days after discontinuation of study medication. Lactating females must agree to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after discontinuation of study medication. Male subjects must refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of study drug. Exclusion Criteria: A history of hepatic decompensation including any episode of variceal bleeding, clinically detectable ascites, or overt hepatic encephalopathy. Status post TIPS (Transjugular Intrahepatic Porto-systemic Shunt) procedure. Evidence of other forms of chronic liver disease including viral hepatitis B or C, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, alpha-1 antitrypsin deficiency, alcoholic hepatitis, hemochromatosis, liver cancer, or history of biliary diversion. Any of the following laboratory values: Serum alanine aminotransferase (ALT) and aspartate aminotransferase levels > 10X upper limits of normal, Serum creatinine ≥ 2.0 mg/dL, Platelet count < 60,000/mm3, Serum albumin ≤ 2.8 g/dL, INR ≥ 1.7, Direct bilirubin ≥ 2.0 mg/dL A MELD score ≥ 15 or Child-Pugh-Turcotte Stage B or C Known positivity for Human Immunodeficiency Virus (HIV) infection Any subject who had major surgery within 8 weeks of Day 1, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study. Weight reduction surgery within the past 3 years. Any subject with current, significant alcohol consumption or a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening will be excluded. Any subject with concurrent infection including diagnoses of fever of unknown origin (FUO) (subjects must be afebrile at the start of therapy). Any history of malignancy, except for the following adequately-treated non metastatic basal cell skin cancer; any other type of skin cancer, except melanoma, that has been adequately treated and has not recurred for at least 1 year prior to enrollment; and adequately treated in situ cervical cancer that has not recurred for at least 1 year prior to enrollment. Participation in an investigational new drug (IND) trial in the 30 days before randomization Clinically significant medical or psychiatric condition considered a high risk for participation in an investigational study. Failure to give informed consent Subjects with known allergies to the study drug or any of its excipients. Is an employee or family member of the investigator or study site personnel. Any subject who cannot undergo an MRI, e.g., due to certain metal or electronic device implants, as determined by the Principal Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GR-MD-02<br>Active | Drug: GR-MD-02<br>* GM-MD-02 active<br>* Other names: galactoarabino-rhamnogalacturonate;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Liver Fibrosis of Corrected T1 (cT1) Mapping (LiverMultiScan -LMS) | Difference in baseline adjusted mean change in liver fibrosis of corrected T1 (cT1) mapping with LiverMultiScan (LMS). LiverMultiScan is CE marked as a class IIa medical device. Corrected T1 (cT1) is a Magnetic Resonance (MR) relaxation parameter/measure from the device.The measure cT1 can be compared across different Magnetic Resonance Imaging (MRI) systems and sites. It is an emerging biomarker for rapid quantification of hepatic fibro-inflammatory disease. In unhealthy tissue, such as in inflamed and fibrotic tissues, measures result in longer cT1-relaxation. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted Change in Liver Stiffness With MR-elastography (MRE) | Baseline-adjusted change in liver stiffness as measured by MR-elastography. Magnetic resonance elastography (MRE) is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of body tissues. Currently, MRE is used to detect stiffening of the liver caused by fibrosis and inflammation in chronic liver disease. Liver stiffness increases with liver damage/disease. | 16 weeks | 
| Baseline-adjusted Change in Liver Stiffness by FibroScan® | Baseline-adjusted change in liver stiffness as measured by FibroScan® scores. FibroScan measures scarring by measuring the stiffness of your liver. The fibrosis result is measured in kilopascals (kPa). It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. | 16 weeks |