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

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

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

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: IDN-6556; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Mary Immaculate Hospital
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Confirmed cirrhosis or suspicion of cirrhosis
  2. Esophageal varices
  3. Ascites
  4. Suspicion of portal hypertension
  5. Hospitalization for liver disease within 60 days of screening
  6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDN-6556; IDN-6556 capsules, 25 mg BID	Drug: IDN-6556; 25 mg BID for 28 days; Other Names: emricasan; PF-03491390
Placebo Comparator: Placebo; Placebo BID	Other: Placebo; Placebo BID for 28 Days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Conatus Pharmaceuticals Inc.
• Investigators: Study Director: Jean L. Chan, MD, Conatus Pharmaceuticals

Publications and helpful links

General Publications

• Shiffman M, Freilich B, Vuppalanchi R, Watt K, Chan JL, Spada A, Hagerty DT, Schiff E. Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2019 Jan;49(1):64-73. doi: 10.1111/apt.15030. Epub 2018 Nov 14.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 4, 2014

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: NAFLD; NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: IDN-6556-06