Non-alcoholic Steatohepatitis
Conditions
Interventions
investigational material(s)
Generic name etc : LJN452
INN of investigational material : Tropifexor
Therapeutic category code : 391 Agents for liver disease
Dosage and Administration for Investigation
Sponsors
Novartis Pharma K. K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: *male/female patients, 18 years or older *written informed consent *Part A and B patients: presence of NASH by histological evidence (liver biopsy obtained 2 years or less prior to randomization) with fibrosis level of F1, F2 or F3 (fibrosis in the absence of cirrhosis) and no diagnosis of chronic liver disease and elevated alanine aminotransferase (ALT) OR phenotypic diagnosis based on elevated ALT, BMI and diagnosis of Type 2 diabetes mellitus (DM) *Part C patients: presence of NASH by histological evidence (liver biopsy obtained during the Screening period or 6 months or less prior to randomization) with fibrosis level of F2 or F3 and no diagnosis of chronic liver disease And ( All Parts): *ALT >= 43 IU/L (males) or >= 28 IU/L (females) *Liver fat equal to or higher than 10% by MRI
Exclusion criteria
Exclusion criteria: *previous exposure to OCA *patients taking prohibited medications *patients taking the following medicines UNLESS on a stable dose (within 25% of baseline dose) for at least 1 month before randomization: (for Part C patients, dose must be stable for at least 1 month prior to biopsy through Screening: anti- diabetic medications, insulin, beta-blockers, thiazide diuretics, fibrates, statins, niacin, ezetimibe, vitamin E (if doses > 200 IU/day; doses > 800 IU/day are prohibited), thyroid hormone, psychotropic medications, estrogen or estrogen containing birth control *pregnant or nursing (lactating) women *current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening *uncontrolled diabetes mellitus *new use of GLP-1 agonists such as liraglutide, exenatide, lixisenatide, albiglutide or dulaglutide within 3 months of screening *presence of cirrhosis *hepatic decompensation or severe liver impairment *previous diagnosis of other forms of chronic liver disease *patients with contraindications to MRI imaging Other protocol defined inclusion/exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Adverse event profile of different doses of LJN452 in patients with NASH [ Time Frame: 12 weeks ] Occurrence of Serious Adverse Event (SAE), Adverse Event (AE) resulting in treatment discontinuation and/or dose reductions, and AE of special interest, from baseline to week 12 efficacy Change in Transaminase levels [ Time Frame: 12 weeks ] To determine the dose relationship of LJN42 on markers of hepatic inflammation in NASH (ALT and AST) Change from baseline in % of fat in the liver assessed using MRI [ Time Frame: 12 weeks ] To determine the dose-response relationship of LJN452 on liver fat content by changes in quantitative MRI | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Change from baseline in weight [ Time Frame: 12 weeks ] To determine the effect of different doses of LJN452 on weight, after 12 weeks of treatment efficacy Change from baseline in biomarker FGF19 [ Time Frame: 6 weeks ] To determine the dose-response relationship of LJN452 on FGF19 over time, a marker of FXR target engagement in the gut. efficacy Change from baseline on on markers of liver fibrosis [ Time Frame: 12 weeks ] To determine the dose-response relationship of LJN452 on markers of liver fibrosis commonly available such as Fibroscan, enhanced liver fibrosis panel (ELF), and fibrosis biomarker test (originally known as Fibrotest/ FibroSure) efficacy Change from baseline on gamma-glutamyl transferase (GGT) [ Time Frame: 12 weeks ] To determine the dose-response relationship of LJN452 on GGT, a marker of cholestasis | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania, South America
Outcome results
None listed