Clinical trial NCT02077374: A Study of IDN-6556 in Subjects With NAFLD and Raised Transaminases
Official title: A Placebo-Controlled, Multicenter, Double-Blind, Randomized Trial of IDN-6556 in Subjects With Non-Alcoholic Fatty Liver Disease and Raised Transaminases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis
Non-alcoholic Fatty Liver Disease
Keywords: NAFLD
NASH
Lead sponsor: Conatus Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-04
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Alanine Aminotransferase (ALT)
timeFrame: Day 28/ET
measure: Relative Percent Change in Alanine Aminotransferase (ALT)
timeFrame: Baseline to Day 28/ET
Secondary outcomes:
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: Day 28/ET
measure: Levels of cCK18/M30
timeFrame: Day 28/ET
measure: Levels of Caspase 3/7 RLU
timeFrame: Day 28/ET
measure: Levels of flCK18/M65
timeFrame: Day 28/ET
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Newport News
country: United States
facility: Mary Immaculate Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital
state: Virginia
Study officials:
affiliation: Conatus Pharmaceuticals Inc.
name: Jean L. Chan, MD
role: STUDY_DIRECTOR
References:
citation: 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.