Study evaluating safety, tolerability and efficacy of the experimental drug EYP001a in patients with non-alcoholic steatohepatitis

Phase 1

Conditions: onalcoholic steatohepatitis with likely stage F2 to F3 fibrosis
MedDRA version: 20.0Level: SOCClassification code 10019805Term: Hepatobiliary disordersSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2018-003119-22-FR

Lead Sponsor: ENYO Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

Inclusion Criteria

1. Provides signed written informed consent and agrees to comply with the study protocol.
2. Is a male or female aged 18 years or older.
3. Has a suspected diagnosis of NASH during the Screening Period (up to 60 days before dosing), defined as follows:
a. The average baseline serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values should be established by at least 2 samples obtained at least 4 weeks and no more than 12 weeks apart. One sample can be obtained from the patient's medical history and 1 sample can be obtained during the Screening Period, or both samples can be obtained during the Screening Period. Unless both samples are within normal ranges, to be eligible for study entry, the difference between the first and second measurement of ALT and AST should be =< 30%. A third sample will be collected if the variability between the first 2 values exceeds the 30% limit. If the third sample exceeds the 30% limit (compared to the first result), the isolated ALT or AST increase shall prompt the search for signs of worsening of liver injury to be further evaluated under Exclusion Criterion 2. If the third sample is within the 30% variability limit, the patient will be eligible for enrollment. If the values of ALT or AST in both samples are within
normal ranges, the variability of the marker is assumed adequate for randomization. Baseline AST values should be >=0.6 x upper limit of normal (ULN) (ie, >20 U/L).
b. Normal average baseline levels of alkaline phosphatase (ALP). Total bilirubin (TBL) levels should be =< 22.2 umol/L (1.3 mg/dL).
c. Liver stiffness compatible with liver fibrosis stage F2 or F3 determined by FibroScan® vibration-controlled transient elastography assessment
cut-off value >= 8.5 kPa.
d. FibroScan controlled attenuation parameter (CAP) for steatosis with cut-off values >300 dB/m.
e. LFC >=10% as measured by MRI PDFF.
4. Is not of childbearing potential (as defined in Inclusion Criterion 5) or, if of childbearing potential, is not pregnant as confirmed by a negative
serum human chorionic gonadotropin test at screening and is not planning a pregnancy during the course of the study.
5. Women of childbearing potential and male patients with female partners must agree to use a dual method of contraception as defined in
the study protocol or practice complete abstinence from sexual intercourse if this is the patient's usual and preferred lifestyle throughout the duration of the study and for 90 days after stopping study drug. Patients who are using hormonal contraceptives should be instructed to use an additional contraceptive measure during 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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Is an employee of a clinical research organization, vendor, or Sponsor involved with this study
2. Shows evidence of worsening liver injury, defined as either an increase of >30% between 2 baseline values of ALT or AST or an increase of >20% between 2 baseline values of TBL or ALP and when such values are above the ULN or associated with clinical signs or symptoms of liver impairment
3. Has known non-NASH liver disease, including, but not limited to, alcoholic liver disease, autoimmune disease, human immunodeficiency virus, hepatitis B virus, active hepatitis C virus (HCV), Wilson's disease, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, drug-induced liver injury, bile duct obstruction, or suspected or known liver cancer
4. Has history of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of esophageal varices
5. Has known history of alcohol abuse or daily heavy alcohol consumption. Has an Alcohol Use Disorders Identification Test-Concise (AUDIT-C) score of >=3 points for men and women AND a full Alcohol Use Disorders Identification Test (AUDIT) score of >=8 points at screening
6. Has Gilbert's syndrome with direct bilirubin >1x ULN
7. Is pregnant or breastfeeding
8. Has clinically relevant immunosuppression, including, but not limited to, immunodeficiency conditions
9. Has a known preexisting medical or psychiatric condition that could interfere with the patient's ability to provide informed consent or participate in study conduct, or that may confound study findings
10. Has, in the opinion of the Investigator, clinically significant cardiovascular or cerebrovascular disease within 90 days prior to the first study drug administration
11. Has participated in any drug study within 90 days prior to the first study drug administration in the current study
12. Has had major surgery within 90 days prior to the first study drug administration in the current study
13. Has a history of relevant drug and/or food allergies
14. Unable to undergo an MRI PDFF due to:
a. Contraindication to MRI examination
b. Severe claustrophobia impacting ability to perform MRI during the study, despite mild sedation/treatment with a short half life (ie, <20
hours) anxiolytic
c. Body weight or girth exceeding the scanner capacities
15. Is using any of the following disallowed medications:
a. Anticancer drug(s), immunomodulator(s), or immunosuppressant(s) within 90 days or 5 half lives prior to screening, whichever is longer, or
any drug historically associated with NAFLD with known liver toxicity for >2 weeks in the year prior to screening
b. Vitamin E (>400 IU/day), glitazones, glucagon-like peptide 1 receptor agonists, ursodeoxycholic acid, or obeticholic acid within 90 days prior
to screening
c. Agents (including herbal over-the-counter weight loss preparations) or medications known to significantly impact body weight within 90 days
prior to screening
d. Statins other than rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, or lovastatin
e. Agents that are substrates for cytochrome P450 (CYP) 2C8 or CYP2C9 and have a narrow therapeutic index
16. Has prior or planned (during the study period) bariatric surgery
17. Has type 1 diabetes mellitus
18. Has type 2 diabetes mellitus and hemoglobin A1c >9.5% or has not been on a stable dose of antidiabetic medication for at least 90 days
prior to screening
19. Has had total body weight loss of >5% within 6 months or since a liver biop

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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