A Proof-of-principle Study of Oral Treatment of Non-alcoholic Steatohepatitis With a Novel PDE4 Inhibitor ASP9831

Protocol for a Phase II, Randomized, Double-blind, Parallel-group, Placebo-controlled, 12-week Treatment, Adaptive Proof-of-principle Study of Twice Daily Oral Dosing of a Novel PDE4 Inhibitor (ASP9831) in Subjects With Non-alcoholic Steatohepatitis (NASH)

The aim of this study is to explore the effect of a new drug (ASP9831) in patients with non-alcoholic steatohepatitis (NASH) by assessing clinical signs, laboratory data and biomarkers during a 12 week treatment period

The study includes an open-label sub-study prior to the main study

Inclusion Criteria:

• NASH, histologically confirmed by a liver biopsy performed within 1 year prior to first dose and randomization
• Elevated serum ALT levels

Exclusion Criteria:

• Hepatic cirrhosis
• Other known cause of liver disease
• Uncontrolled diabetes mellitis type 2, i.e. HbA1c > 8.5%
• Positive history of tuberculosis or a positive PPD skin test which is not explained by previous BCG vaccination
• History of excessive alcohol abuse within 5 years prior to screening or a current average alcohol intake of more than 20 g/day (2 units) for females or more than 30 g/day (3 units) for males
• Subject has used drugs associated with steatohepatitis within 6 months prior to screening (corticosteroids, high dose estrogens, methotrexate, amiodarone, anti-HIV drugs, tamoxifen)