Evaluation of the Physiological Stability Variability and Robustness of NIS4

Study Overview
=================
Brief Summary
-----------------
Patients at higher risk of progression to cirrhosis and clinical deleterious outcomes are those that have a high grade of necroinflammation together with significant fibrosis. This defines a level of disease severity which is called at-risk NASH. Currently registrational trials for NASH include only patients with at-risk NASH so it is predictable that when a drug will be approved for NASH it will be in patients with at-risk NASH. It is therefore important to be able to diagnose non-invasively patients with at-risk NASH. Also, the use of NIS4 in clinical trials or in the clinic has the potential to significantly reduce unnecessary liver biopsies by identifying patients with a lower risk of disease progression. GENFIT, a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and chronic liver diseases, is developing an in vitro diagnostic test for at-risk NASH. The test is calledNIS4™ and integrates four independent biomarkers - miR-34a-5p, A2M, YKL-40 and HbA1c. The output is a score from 0 to 1 with threshold values that identify patients at low risk and high risk of at-risk NASH with intermediate values representing indeterminate results. The objective of the program is to complete the development of the predictive and usable NIS4 score and to evaluate the impact of fasting or not fasting on the physiological stability, variability and robustness of circulating biomarkers for the diagnosis of non-alcoholic steatohepatitis over a 30-day period.

Official Title
-----------------
Evaluation of the Physiological Stability Variability and Robustness of NIS4,a Serum Biomarker for the Diagnosis of Non-alcoholic Steaohepatitis

Conditions
-----------------
Evaluate the Physiological Stability of NIS4 Biomarker Between the Fed and Fasting State in Patients With the Target Condition (NAFLD)

Intervention / Treatment
-----------------
* Diagnostic Test: Blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically documented steatohepatitis (NASH) with at least minimal (grade 1) hepatocyte ballooning and inflammation on a biopsy performed in the past year. OR, if a biopsy is not available: Presence of metabolic risk factors (see below) AND Documentation of steatosis on imaging (hepatic ultrasound, CT scan or MRI) AND Increased ALT >30 IU/L OR liver stiffness >5 kPa on Fibroscan Metabolically stable condition, in particular no weight change >5% in the past 6 months, anticipated stable diabetic therapy during the study period No other identifiable cause of liver disease Patients affiliated to French social security. Written informed consent signed by the patient Exclusion Criteria: Patient with Hepatitis B or C. Presence of any other form of chronic liver disease Average alcohol consumption greater than 20 g/day for females and 30 g/day for males in the preceding 6 months or history of sustained excessive consumption of alcohol in past 5 years. Severely uncontrolled diabetes (HbA1c>9.5%) Recent (within 12 months) or concomitant use of agents known to cause hepatic steatosis (long-term systemic corticosteroids [>10 days], amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid). Recent (within 3 months) change in dose/regimen or introduction of Vitamin E (at a dose ≥400 IU/day), betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin or pentoxifylline. HIV infection. Person not fasted 12 hours (T10, T12, D0). Substantial diet modification in the 4 months prior to inclusion. Patients judged by the investigator to be unsuitable for inclusion in the study (e.g., judged by the physician as unlikely to be compliant with the study protocol). Pregnant or breastfeeding women. Patient under legal protection measure. Patient is a participating in another research study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 88 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Steatohepatitis (NASH)<br> | Diagnostic Test: Blood test<br>* Whenever possible, samples will be collected by the nurse in the patient's home, according to the study visit schedule. However, if this is not possible, patients will be asked to come in for sample collection at another mutually convenient time at the CERBA ALLIANCE LABORATORY closest to the patient's address. Venous blood will be drawn on each visit.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The stability of the Non-invasive diagnostic test for steatohepatitis (NIS) 4 score and its individual components between the fed and fasting state by the the measurement of the four biomarkers involved in the calculation of NIS4 score |  | After dinner , 10 hours post-prandial and 12 hours post-prandial |