Non-alcoholic Steatohepatitis (NASH) MedDRA version: 9.1 Level: LLT Classification code 10053219 Term: Non-alcoholic steatohepatitis
Conditions
Sponsors
Astellas Pharma Europe B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Part 1: 1. Subject has signed written informed consent prior to screening 2. Subject is male or female and 18 years of age or above 3. For Part 1a: Subject has NASH, fibrosis stage F3 (zone 3 perisinusoidal/pericellular fibrosis and portal fibrosis with focal or extensive bridging fibrosis), histologically confirmed by a liver biopsy performed within 1 year prior to first dose For Part 1b: Subject has NASH, fibrosis stage F0-F3, histologically confirmed by a liver biopsy performed within 1 year prior to randomization 4. Subject has serum ALT levels at screening below 300 U/l according to central laboratory analysis 5. Subject has had elevated serum ALT levels on two occasions tested within 1 year prior to screening according to local laboratory normal ranges Inclusion Criteria Part 2: 1. Subject has signed written informed consent prior to screening 2. Subject is male or female and 18 years of age or above 3. Subject has NASH, fibrosis stage F0-F3, histologically confirmed by a liver biopsy performed within 1 year prior to randomization 4. Subject has elevated serum ALT levels at screening of at least 1.5 x the upper limit of normal range with a maximum of 300 U/l according to central laboratory analyses. 5. Subject has had elevated serum ALT >1.5 ULN or >60 IU/L (local laboratory) on one occasion in the past 6 months and no documented normal value in the past year 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
Exclusion criteria: 1. Subject is diagnosed with hepatic cirrhosis 2. Subject has confirmed positive HCV and/or positive HCB serology 3. Subject has known genetic or secondary hemochromatosis 4. Subject has other known cause of liver disease (autoimmune, viral, genetic, drug induced, alcoholic liver disease or storage disease) 5. Subject has an unstable metabolic condition: i.e. weight change > 5% in the 6 months prior to screening and/or diagnosis of diabetes mellitus type 2 within 4 months prior to screening and/or initiation and subsequent continuous use of anti-diabetic drugs (including insulin sensitizing agents), anti-hypertensives and / or lipid-lowering drugs within 4 months prior to screening 6. Subject has uncontrolled diabetes mellitus type 2, i.e. HbA1c > 8.5% 7. Subject suffers from clinically significant gastrointestinal disease, or has a history of inflammatory bowel disease (Crohn's disease, ulcerative colitis and undetermined inflammatory colitis) or has a currently symptomatic gastric ulcer or erosive gastritis 8. Irritable bowel syndrome 9. Subject has known lipodystrophy 10. Subject has had a malignancy in the last 10 years, except for adequately treated basal or squamous cell carcinoma of the skin 11. Subject has known HIV infection 12. Subject has had previous bowel resection 13. Subject has a positive history of tuberculosis or a positive PPD skin test which is not explained by previous BCG vaccination 14. Subject has any other disorder that is uncontrolled by therapy and clinically significant as deemed relevant by the investigator 15. 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 16. Female subject is pregnant, lactating or pre-menopausal with positive serum pregnancy test (hCG) or has an intention of becoming pregnant and/or does not use a medically acceptable method of birth control 17. Subject has used drugs associated with steatohepatitis within 6 months prior to screening (corticosteroids, high dose estrogens, methotrexate, amiodarone, anti-HIV drugs, tamoxifen) 18. Subject used other PDE4 inhibitors within 6 months prior to screening 19. Subject started or changed the dose of one or more of the following drugs/food supplements within 1 month before randomization: insulin sensitizing agents (e.g. biguanides, thiazolinediones), ursodeoxycholic acid, anti-obesity drugs (e.g. orlistat, sibutramin, rimonabant), pentoxifylline, phosphatidylcholin, ginseng, selenium, vitamin C, vitamin E 20. Subject uses concomitant medications which are mainly metabolized by CYP2C8/9 and which have a narrow safety margin (warfarin, phenytoin, paclitaxel and tolbutamide)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Percentage change in serum ALT at the end of treatment at 12 weeks compared to baseline;Main Objective: Part 1: Objective: To explore exposure to ASP9831 in patients with Non-alcoholic Steatohepatitis (NASH) and to compare the data with healthy volunteer data Part 2: Primary objective: To study the effect of a 12 week treatment with two dose levels of ASP9831 compared to placebo on liver injury by assessing serum levels of Alanine Aminotransferase (ALT) in subjects with NASH;Secondary Objective: Part 2: Secondary objectives: • To study the safety of two dose levels of ASP9831 compared to placebo in subjects with NASH • To perform an exploratory analysis of o the effect of ASP9831 on hepatic steatosis o the effect of ASP9831 on liver inflammation and vascular damage o the effect of ASP9831 on other liver injury markers o the effect of ASP9831 on liver fibrosis o the effect of ASP9831 on insulin resistance o the effect of ASP9831 on clinical symptoms o the pharmacokinetics and the pharmacokinetic / pharmacodynamic relationships of ASP9831 in the study population | — |
Countries
Belgium, Czech Republic, France, Germany, United Kingdom
Outcome results
None listed