Non-alcoholic Steatohepatitis (NASH) MedDRA version: 20.1 Level: PT Classification code 10029530 Term: Non-alcoholic fatty liver System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: EDP-305
Product Code: EDP-305
Pharmaceutical Form: Tablet
INN or Proposed INN: Not available
CAS Number: 1933507-63-1
Sponsors
Enanta Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive 2. Male or female with presence of NASH by: - Histologic evidence on a historical liver biopsy within 24 months of Screening consistent with NASH with fibrosis (no cirrhosis), and elevated ALT at Screening OR - Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes AND - Screening MRI PDFF with >8% steatosis 3. Body mass index (BMI) >25 kg/m2. NOTE: for Asian-Americans, BMI >23 kg/m2 4. 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. 5. Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305. 6. All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug. 7. Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug. 8. Subject must be willing and able to adhere to the assessments, visit schedules, prohibitions and restrictions, as described in this protocol. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Laboratory Screening Results: - Total bilirubin >ULN (normal range 0.2–1.2 mg/dL) - Total white blood cells (WBC) 1.2 - Creatine kinase above the upper limit of normal (ULN) except when in relation with intense exercise - Serum creatinine >2 mg/dL or clearance creatinine 2 × ULN 14. Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 µmol/L) 15. Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening 16. Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening) 17. History of regular alcohol consumption exceeding 14 drinks/week for females and 21 drinks/week for males within 6 months of Screening. 18. Subject has received an investigational agent or vaccine within 30 days, or a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug. 19. Clinically significant electrocardiogram abnormalities or QTcF greater than 450 ms for males and 470 ms for females at either Screening or Baseline, or any prior history of QT abnormality 20. Use of cytochrome P450 (CYP)3A4 and P-glycoprotein (P-gp) inducers and inhibitors within 14 days prior to the first dose of study medication and throughout study duration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate change in alanine aminotransferase (ALT) levels - To evaluate the safety and tolerability of EDP-305 ; Secondary Objective: - To evaluate the effect of EDP-305 on liver fat - To evaluate the effect of EDP-305 on fibrosis (liver stiffness) - To evaluate the effect of EDP-305 on noninvasive liver fibrosis markers - To evaluate the effects of EDP-305 on lipids - To evaluate the effects of EDP-305 on glucose metabolism - To evaluate the effects of EDP-305 on inflammatory markers - To evaluate the pharmacokinetics (PK) of EDP-305 and its metabolites in plasma - To evaluate the effect of EDP-305 on body weight - To evaluate the effect of EDP-305 on waist to hip (WTH) ratio - To evaluate the pharmacodynamics of EDP-305 ; Primary end point(s): - Change from baseline in ALT levels at Week 12 - Frequency of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation through Week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from Baseline in percentage of fat in the liver as assessed by magnetic resonance imaging-estimated proton density fat fraction (MRI PDFF) at Week 12 - Change from Baseline in liver stiffness as assessed by magnetic resonance elastography (MRE) at Week 12 - Change from Baseline of noninvasive liver fibrosis markers (Enhanced Liver Fibrosis [ELF] panel) and PRO C3 at Week 12 - Change from Baseline in non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), AST to Platelet Ratio Index (APRI), and fibrosis 4 (FIB-4) at Week 12 - Change form Baseline in triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), adiponectin and apolipoproteins (Apo)A1, B, C3 at Week 12 - Change from Baseline in fasting glucose and insulin, homeostasis model assessment (HOMA) index (in nondiabetic subjects) and glycated hemoglobin (HbA1c) in subjects with Type 2 diabetes mellitus (T2DM) at Week 12 - Change from Baseline in fibrinogen, CRP, IL6, IL1ß, TNF-a, TNF-ß , alpha2 macroglobulin and haptoglobin levels at Week 12 - Pharmacokinetic parameters of EDP-305 (and metabolites): Cmax, tmax, and AUClast - Change from Baseline in body weight at Week 12 - Change in WTH ratio at Week 12 - Pharmacodynamic parameters of EDP-305: FGF19, C4, and bile acid (BA) at Week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Canada, France, Germany, New Zealand, United Kingdom, United States
Contacts
Public ContactNathalie Adda
Enanta Pharmaceuticals Inc.,
Outcome results
None listed