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) - ASTER

Phase 1

• Conditions: on-alcoholic Steatohepatitis (NASH); MedDRA version: 9.1Level: LLTClassification code 10053219Term: Non-alcoholic steatohepatitis

• Registration Number: EUCTR2007-002114-19-FR
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-12-27
• Study Completion: 2010-10-08
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

Main criteria for inclusion:
• Subject has signed written informed consent prior to screening
• Subject is male or female and 18 years of age or above
• For Part 1: Subject has NASH, fibrosis stage F3, histologically confirmed by a liver biopsy performed within 1 year prior to first dose
• For Part 2: Subject has NASH, fibrosis stage F0-F3, histologically confirmed by a liver biopsy performed within 1 year prior to randomization
• Subject has elevated serum ALT levels at screening of at least 1.5x the upper limit of normal range with a maximum of 300 U/l according to central laboratory analysis
• Subject has had elevated serum ALT levels of at least 1.5x the upper limit of normal range on two occasions tested and no ALT levels below 1.5x the upper limit of normal range within 1 year prior to screening according to local laboratory normal ranges
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Subject is diagnosed with hepatic cirrhosis
• Subject has other known cause of liver disease (autoimmune, viral, genetic, drug induced, alcoholic liver disease or storage disease)
• Subject has an unstable metabolic condition: i.e. diagnosis of diabetes mellitus type 2 and / or hyperlipidemia with hypertension within 6 months prior to screening; use of lipid lowering drugs, anti-hypertensives and / or anti-diabetics (including insulin sensitizing agents) started within 6 months prior to screening; weight change > 5% in the 6 months prior to screening
• Subject has uncontrolled diabetes mellitus type 2, i.e. HbA1c > 8.5%
• Subject has a positive history of tuberculosis or a positive PPD skin test which is not explained by previous BCG vaccination
• Subject has a 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)
• Subject uses concomitant medications which are mainly metabolized by CYP2C8/9 and which have a narrow safety margin (warfarin, phenytoin, paclitaxel and tolbutamide)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified