A randomized, double-blind, placebo controlled, 2- part, adaptive design, multicenter 12-week study to assess safety, tolerability and efficacy of LJN452 in patients with non-alcoholic steatohepatitis (NASH)
- Conditions
- Extra amount of fat in liver cells that is not caused by alcohol use10019654
- Registration Number
- NL-OMON46032
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
- Written informed consent must be obtained before any assessment is performed
- Male and female patients 18 years or older (at the time of the screening visit)
- Presence of NASH as demonstrated by ONE of the following:
o Histologic evidence of NASH based on liver biopsy obtained 2 years or less before randomization with a diagnosis consistent with NASH, fibrosis level F1, F2 or F3 (i.e. fibrosis in the absence of established cirrhosis), no diagnosis of alternative chronic liver diseases AND
o ALT * 43 IU/L (males) or * 28 IU/L (females)
OR
o Phenotypic diagnosis of NASH based on presence of ALL THREE of the following:
- ALT * 60 IU/L (males) or * 40 IU/L (females) AND
- BMI * 27 kg/m2 (in patients with a self-identified race other than Asian) or *23 kg/m2 (in patients with a self-identified Asian race) AND
- Diagnosis of Type 2 diabetes mellitus by having either:
* HbA1C * 6.5% or
* Drug therapy for Type 2 diabetes mellitus
- Liver fat * 10% at screening as determined by the central MRI laboratory
- Patients must weigh at least 40 kg (88 lb) and no more than 150 kg (330 lb) to participate in the study
- Previous exposure to obeticholic acid (OCA)
- Patients taking medications prohibited by the protocol
- 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 (significant alcohol consumption is defined as more than 20 g/day in females and more than 30 g/day in males, on average) and/or a score on the AUDIT questionnaire *8
- Uncontrolled diabetes defined as HbA1c * 9.5% within 60 days prior to enrollment
- Presence of cirrhosis on liver biopsy or clinical diagnosis
- Clinical evidence of hepatic decompensation or severe liver impairment
- Previous diagnosis of other forms of chronic liver disease
- Patients with contraindications to MRI imaging
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective of the study is to determine safety and tolerability of<br /><br>different doses of LJN452 by monitoring adverse events up to the end of<br /><br>the study. Moreover, the study will determine the dose-response relationship of<br /><br>LJN452 on markers of hepatic inflammation in NASH by changes in ALT and AST<br /><br>from baseline to Week 12. The study will also determine the dose-response<br /><br>relationship of LJN452 on liver fat content by changes in quantitative MRI<br /><br>determined fat.</p><br>
- Secondary Outcome Measures
Name Time Method