A 2 part clinical study that will evaluate the safety and effectiveness of LJN452A to treat patients with fatty liver disease for a period of 12 weeks. The first part will be used for LJN452 dose selection for the second part of the study.

Phase 1

• Conditions: on-alcoholic Steatohepatitis (NASH); MedDRA version: 20.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2015-005215-33-SK
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-05-10
• Last Update Posted: 11 May 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 345

Inclusion Criteria

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)

Diagnosis of NASH:

Parts A&B:
Presence of NASH as demonstrated by ONE of the following:
- 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

Part C (All patients): Adequate liver biopsy sample for evaluation by
Central Reader to confirm Histologic evidence of NASH based on liver
biopsy obtained during the Screening period or within 6 months before
randomization with a diagnosis consistent with NASH, fibrosis level F2 or
F3, and no diagnosis of alternative chronic liver diseases. Permitted
therapy must be stable as outlined in Table 5-5 (from 1 month prior to
biopsy up to and including screening)

AND (all parts)
ALT = 43 IU/L (males) or = 28 IU/L (females)

OR (for Parts A and B only)
Phenotypic diagnosis of NASH based on presence of ALL THREE of the following:
o ALT = 43 IU/L (males) or = 28 IU/L (females) AND
o 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
o 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
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 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 155

Exclusion Criteria

Previous exposure to an FXR agonist including tropifexor

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 clinical trial of medicinal product
• Study Design: Not specified