A Placebo-Controlled Study to Assess the Safety and Efficacy of Different Doses of EDP-305 in Patients with Non-Alcoholic Steatohepatitis (NASH) Confirmed by a Liver Biospy
- Conditions
- on-alcoholic Steatohepatitis (NASH)MedDRA version: 22.0Level: LLTClassification code 10029530Term: Non-alcoholic fatty liverSystem Organ Class: 100000004871Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2019-003876-38-DE
- Lead Sponsor
- Enanta Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 336
• Male and female subjects, of all ethnic origins, between the ages of 18 and 75 years, inclusive.
• Subjects of all ethnic origins should have a Body Mass Index (BMI) > 25 kg/m2 and =45 except for Asian subjects who qualify for the study with BMI > 23kg/m2.
• Histological evidence of definite NASH based on NASH Clinical Research Network (CRN) criteria obtained from assessment of a liver biopsy by the central histopathologist.
• Non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2).
• Fibrosis stage 2 or 3 using the NASH CRN Histologic Scoring System.
• For subjects taking Vitamin E or pioglitazone, the following three criteria apply:
-subjects must have been on a stable dose for at least 12 weeks prior to the qualifying biopsy, and
-treatment with Vitamin E or pioglitazone cannot have started after the qualifying biopsy, and
-it is expected that subjects will continue on the same dosing regimen throughout study participation unless required to adjust doses due to safety reasons.
• Subjects who had previously been taking Vitamin E or pioglitazone (but are no longer taking either one), must have discontinued Vitamin E or pioglitazone a minimum of 12 weeks prior to the qualifying biopsy.
• Weight change <5% after the qualifying biopsy.
• Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA, and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative.
• For hypertensive patients, blood pressure should be controlled by
stable dose of anti-hypertensive medication for at least 8 weeks prior
to Screening with the intention to keep the regimen stable during the
study.
• A woman of childbearing potential who is sexually active with a male
must agree to use two effective methods of contraception from the date
of Screening until 30 days after the last dose of study drug.
• A male subject who has not had a vasectomy and is sexually active
with a woman of childbearing potential must agree to use effective
contraception from the date of Screening to 90 days after the last dose
of study drug.
• Aspartate aminotransferase > 30 IU/L
• Magnetic resonance imaging - proton density fat fraction =8%
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 269
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 67
• Laboratory Screening results as indicated below:
- Total white blood cells (WBC) <3000 cells/mm3
- Absolute neutrophil count (ANC) <1500 cells/mm3
- Platelet count <140,000/mm3
- International Normalized Ratio, INR >1.2 (unless due to use of
anticoagulants)
- Estimated glomerular filtration rate (eGFR) < 60 mL/min according to
the Modification of Diet in Renal Disease (MDRD) equation
- Aspartate aminotransferase =5× upper limit of normal (ULN)
- Alanine aminotransferase =5× ULN
- Alkaline phosphatase = 2x ULN
- Total bilirubin > 1.5 times ULN during Screening.
• Pregnant or nursing females.
• MELD: Model for End-stage Liver Disease score >12.
• Clinical or laboratory evidence of known chronic liver disease such as
alcoholic liver disease, primary biliary cholangitis, primary sclerosing
cholangitis, autoimmune hepatitis, Wilson disease, iron overload, alpha-
1-antitrypsin deficiency, drug-induced liver injury, known or suspected
hepatocellular carcinoma.
• History of acute liver complications due to gallstones (e.g., acute
cholecystitis or acute biliary obstruction), unless the subject has had a
cholecystectomy (more than 12 weeks prior to Screening).
• History of liver transplant, or current placement on a liver transplant
list.
• Hepatorenal syndrome (type I or II).
• Prior variceal hemorrhage, uncontrolled encephalopathy, liver cirrhosis
Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites
within the previous 26 weeks of Screening and/or histological presence
of liver cirrhosis.
• Prior or planned ileal resection, or prior or planned bariatric surgery.
• Subjects with clinically or otherwise documented cardiovascular or
cerebrovascular disease including clinically significant anomalies of
rhythm or pattern of ECG, that in the judgement of the Principal
Investigator could affect the safety of the subject or their ability to
comply with the study requirements.
• Glycated hemoglobin (HbA1c) = 9.5% within 60 days prior to Day 1.
• Use of a new antidiabetic regimen in the months prior to Screening,
including metformin, glucagon-like peptide-1 (GLP-1) agonists, sodium
glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, or dipeptidyl
peptidase 4 (DPP4) inhibitors, insulin or peroxisome proliferatoractivated
receptor ? agonists (e.g. pioglitazone or rosiglitazone). For
pre-existing antidiabetic treatment, subjects should be on a stable dose
of antidiabetic drugs: (1) for at least 8 weeks (for metformin and/or
sulfonylureas), (2) 12 weeks (for SGLT2 or DPP4 inhibitors), or (3) 12
weeks (for GLP-1 receptor agonists and thiazolidinediones) prior to
Screening with the intention to keep the regimen stable during the
study.
• Use of a new statin regimen or other lipid lowering agents from 12
weeks prior to Screening.
• Use of a new fibrate regimen from 12 weeks prior to Screening.
• Subjects with contraindications to MRI imaging, or not being able to
have the MRI performed.
• Subject has received any investigational agent (including
investigational vaccine) or biological product within 30 days or 5 times
the half-life (whichever is longer) prior to the planned first dose of study
drug.
• Use of an experimental or approved treatment for NASH within 26
weeks of Screening.
• Prior use of obeticholic acid (OCA) within 26 weeks of Screening
and/or concurrent treatment with OCA (or any other farnesoid X
receptor agonists).
• Use of systemic immunosuppressant (e.g., corticosteroids) for more
than 4 weeks in duration within 1 y
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