To assess the safety and tolerability profile of LJN452 and to determine the early hepatic response to different doses of LJN452 in patients with phenotypic non-alcoholic steatohepatitis (NASH). Data from this study will be used to support further…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to determine safety and tolerability of
different doses of LJN452 by monitoring adverse events up to the end of
the study. Moreover, the study will determine the dose-response relationship of
LJN452 on markers of hepatic inflammation in NASH by changes in ALT and AST
from baseline to Week 12. The study will also determine the dose-response
relationship of LJN452 on liver fat content by changes in quantitative MRI
determined fat.
Secondary outcome
- To determine the effect of different doses of LJN452 on anthropometric
assessments (weight, BMI, waist-to-hip (WTH) ratio) after 12 weeks of treatment
- To determine the dose-response relationship of LJN452 on FGF19 over time, a
marker of FXR target engagement in the gut, and C4, a marker of hepatic target
engagement
- To determine the dose-response relationship of LJN452 on markers of liver
fibrosis commonly available such as Fibroscan® (in a subset of patients),
enhanced liver fibrosis panel (ELF), and fibrosis biomarker test (originally
known as Fibrotest®/ FibroSure®)
- To determine the dose-response relationship of LJN452 on GGT, a marker of
cholestasis
- To determine the effect of LJN452 on fasting lipid profile To determine the
pharmacokinetics (PK) of LJN452
- To determine the effect of LJN452 compared to placebo with respect to
occurrence of potential itch based on a visual analog scale (VAS) rating scale
- To determine effects of LJN452 on primary endpoints in the subset of patients
who have historical biopsy data, both overall and by subsets defined by
fibrosis score and/or NAS score as feasible (based on the extent of available
data)
Background summary
The purpose of the study is to learn whether it is safe to treat patients who
have NASH with the study drug LJN452. The study will also learn about the
effects of different doses of LJN452 on markers of liver swelling in patients
with NASH.
The second purpose is the examination of biomarkers to help answer scientific
questions related to LJN452 effect on cells or organs in the body, as well as
impact on the disease. These samples will also be used to try to understand the
disease better
In addition, these samples help to understand how the body absorbs,
distributes, breaks down and gets rid of LJN452. This is commonly referred to
as pharmacokinetics.
Study objective
To assess the safety and tolerability profile of LJN452 and to determine the
early hepatic response to different doses of LJN452 in patients with phenotypic
non-alcoholic steatohepatitis (NASH). Data from this study will be used to
support further development of LJN452 in the treatment of patients with NASH
Study design
This is a randomized, double-blind, placebo-controlled, multicenter,
parallel-group, dose finding, 2-part, adaptive, 12-week study to assess the
safety, tolerability and efficacy of four doses of LJN452 as compared to
placebo in patients with non-alcoholic steatohepatitis (NASH).
Intervention
LJN452 10 *g, 30 *g, 60 *g, 90 *g or matching placebo treatment
Study burden and risks
Following the baseline visit, the patiënt will return to the study center at
regular intervals to have their condition monitored and to receive new bottles
with study medication. If participating in Part A of the study, the patient
will return 1, 2, 4, 6, 8, and 12 weeks after starting study medication. If the
patient will participate in Part B of the study, the patient will return 2, 4,
6, 8, and 12 weeks after starting study medication.
Assessments during study visit:
- Blood pressure, pulse
- Weight, waist and hip measurements
- Physical exam:
- ECG
- Questionnaires
- Blood samples
- Urine tests
- Pharmacokinetic blood samples:
- Fibroscan®:
- MRI
- Exploratory biomarker (genetic test)
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
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)
- 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
Exclusion criteria
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-005215-33-NL |
| ClinicalTrials.gov | NCT02855164 |
| CCMO | NL57299.078.16 |