A Study of IDN-6556 in Subjects With NAFLD and Raised Transaminases

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of IDN-6556 compared to placebo in patients with diagnosed fat deposits in their liver (not caused by alcohol) and with abnormal liver tests

Detailed Description
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This is a double-blind, randomized study to evaluate the effects of IDN-6556 on serum transaminases and pharmacodynamics of IDN-6556 in subjects with non-alcoholic fatty liver disease with elevated alanine aminotransferase.

Official Title
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A Placebo-Controlled, Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects With Non-Alcoholic Fatty Liver Disease and Raised Transaminases

Conditions
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Nonalcoholic Steatohepatitis, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: IDN-6556
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the study Diagnosis of non-alcoholic fatty liver disease (NAFLD) as evidenced by imaging or other diagnostic assessments Alanine aminotransferase (ALT) levels ≥1.5 x ULN on at least two occasions, seven or more days apart, during the Screening period alpha-fetoprotein (AFP) ≤ 100 ng/mL Hemoglobin ≥10 g/dL, a platelet count ≥ 100 x 10^9/L, and a white blood cell count ≥ 3.0 x 10^9/L If on metformin, sulfonylureas, statins, or fibrates, subjects must be on a stable dose of these drugs for at least three months prior to Screening and during the study Exclusion Criteria: Known infection with HIV, HCV, or HBV Decompensated or severe liver disease as evidenced by one or more of the following: Confirmed cirrhosis or suspicion of cirrhosis Esophageal varices Ascites Suspicion of portal hypertension Hospitalization for liver disease within 60 days of screening Bilirubin >2 x ULN, or ALT or AST > 10 x ULN Inflammatory bowel disease Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA) Hepatocellular carcinoma (HCC) at entry into the study History of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal insufficiency, and/or serious psychiatric disease, that, in the opinion of the Investigator would preclude the subject from participating in and completing the study History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 4-ounce glasses of wine or 14 12-ounce cans/bottles of beer or wine coolers), or other substance abuse within the prior two years

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDN-6556<br>IDN-6556 capsules, 25 mg BID | Drug: IDN-6556<br>* 25 mg BID for 28 days<br>* Other names: PF-03491390;|
| Placebo Comparator: Placebo<br>Placebo BID | Other: Placebo<br>* Placebo BID for 28 Days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alanine Aminotransferase (ALT) | Mean change in alanine aminotransferase (ALT) from Baseline to Day 28/ET between IDN-6556 vs Placebo | Day 28/ET | 
| Relative Percent Change in Alanine Aminotransferase (ALT) | Back transformation from log-transformed analysis results to original scale in alanine aminotransferase (ALT) from Baseline to Day 28/ET between IDN-6556 vs Placebo | Baseline to Day 28/ET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aspartate Aminotransferase (AST) | Difference in the change in aspartate aminotransferase (AST) from Baseline to Day 28/ET in units per liter (U/L) between IDN-6556 and placebo. | Day 28/ET | 
| Levels of cCK18/M30 | Difference in the change in Caspase-cleaved cytokeratin serum levels (cCK18/M30) in units per liter (U/L) from baseline to Day 28/ET between IDN-6556 and placebo | Day 28/ET | 
| Levels of Caspase 3/7 RLU | Difference in the change of caspase 3/7 (Relative Light Units) from baseline to Day 28/ET between IDN-6556 and Placebo | Day 28/ET | 
| Levels of flCK18/M65 | Difference in the change in full-length cytokeratin 18 (flCK18/M65) in units per liter (U/L) from Baseline to Day 28/ET between IDN-6556 and placebo | Day 28/ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, NASH