A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis

A Phase 2 Dose Ranging, Randomized, Double Blind, and Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis (NASH)

A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: EDP-305 Dose 1; Drug: EDP-305 Dose 2

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6T OG1
      • Aggarwal and Associates Limited
    • Toronto, Ontario, Canada, M6H3M1
      • Toronto Liver Centre
  • Quebec
    • Montreal, Quebec, Canada, H2K 1H2
      • Clinique de recherche Medpharmgene
    • Montreal, Quebec, Canada, H4A 3JI
      • Chronic Viral Illness Service McGill University Health Center/Royal Victoria
• France
  • Paris, France, Cedex 13
    • Hôpital Pitié Salpetrière
  • Pessac, France, 33604
    • CHU de Bordeaux - GH Sud - Hoital Haut Leveque
  • Strasbourg, France, 67000
    • CHU de Strasbourg - Nouvel Hôspital Civil
• New Zealand
  • Auckland, New Zealand, 1010
    • Auckland Clinical Studies Limited
• Puerto Rico
  • San Juan, Puerto Rico, PR 00909
    • Latin Clinical Trial Center
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrookes Hospital (AH)-Cambridge University Hospitals NHS Foundation Trust
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Nottingham University Hospitals NHS Trust
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Radiant Research Incorporated
    • Mesa, Arizona, United States, 58206
      • Central Arizona Medical Associates
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Specialty Building
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Chula Vista, California, United States, 91911
      • estudy site - Chula Vista
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Fresno, California, United States, 93720
      • Fresno Clinical Research Center (FCRC)
    • La Jolla, California, United States, 92037
      • UCSD Altman Clinical and Translational Research Institute
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
    • San Clemente, California, United States, 92673
      • Southern California Transplantation Institute Research Foundation
    • San Diego, California, United States, 92114
      • Precision Research Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates
    • Colorado Springs, Colorado, United States, 80909
      • Clinical Research Advantage, Inc. / Colorado Springs Family Practice
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology,P.C.
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32226
      • Jacksonville Center for Endoscopy - Southside ; Borland Groover Clinic
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research, LLC.
    • Miami, Florida, United States, 33134
      • Research Associates of South Florida, LLC
    • Miami, Florida, United States, 33030
      • Homestead Medical Research
    • Miami, Florida, United States, 33144
      • Florida Advanced Medical Research, Inc.
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center, Inc
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions Inc.
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Feinberg School of Medicine Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kansas
    • Shawnee Mission, Kansas, United States, 66217
      • WestGlen Gastrointestinal Consultants, PA
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Oshsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates, PA
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
      • AGA Clinical Research Associates, LLC
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health Inc.
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • NYU Langone Medical Center - The Center for Musculoskeletal Care (CMC)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center Transplant Center/Center for Liver Disease
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Huntersville, North Carolina, United States, 28078
      • Carolinas Center for Liver Disease / Carolinas Health Care System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center - Center for Liver Diseases
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Health Science Center
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research, PLLC
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
    • Garland, Texas, United States, 75044
      • DHAT Research Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78229
      • Radiant Research, Inc.
  • Utah
    • Layton, Utah, United States, 84041
      • Wasatch Peak Family Practice/Radiant Research, Inc
    • Murray, Utah, United States, 84123
      • Radiant Research, Inc.
  • Virginia
    • Gainesville, Virginia, United States, 20155
      • Gastroenterology Associates, PC
    • Newport News, Virginia, United States, 23602
      • Bon Secours St. Mary's Hospital of Richmond, Inc
    • Reston, Virginia, United States, 20191
      • The Gastroenterology Group, PC
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98104
      • University of Washington / Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center-Swedish Organ Transplant and Liver Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System - Franciscan Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• An informed consent document must be signed and dated by the subject
• Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive

• 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 AND Screening MRI PDFF with >8 % steatosis OR
  • Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes AND Screening MRI PDFF with >8 % steatosis
• Body mass index (BMI) >25 kg/m2; for Asian-Americans, BMI >23 kg/m2
• 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.
• Subject must be willing and able to adhere to the assessments, visit schedules, prohibitions and restrictions, as described in this protocol

Exclusion Criteria:

• Laboratory Screening Results:

  • Total bilirubin > ULN (normal range 0.2-1.2 mg/dL)
  • Total white blood cells (WBC) <3,000 cells/mm3
  • Absolute neutrophil count (ANC) <1,500 cells/mm3
  • Platelet count <140,000/mm3
  • Prothrombin time (international normalized ratio, INR) > 1.2
  • Creatine kinase above the upper limit of normal (ULN) except when in relation with intense exercise
  • Serum creatinine >2 mg/dL or creatinine clearance <60 ml/min (based on Cockroft Gault method)
• Known history of alpha-1-antitrypsin deficiency
• Use of an experimental treatment for NASH within the past 6 months
• Use of immunosuppressant (eg, corticosteroids) for more than 2 weeks in duration within 1 year prior to Screening and during the course of the study
• Use of experimental or unapproved drugs within a year of Screening
• Any other condition(s) (including cardiovascular diseases) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI)
• Pregnant or nursing females
• Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score ≥ 15
• Clinical suspicion of advanced liver disease or cirrhosis
• Coexisting liver or biliary diseases, such as primary sclerosing cholangitis (PSC), choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis
• Suspicion of cancer (eg, liver cancer) with the exception of basal cell carcinoma that has been resected
• Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2xULN
• Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)
• Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
• Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening)
• 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. NOTE: Flu vaccine will be allowed upon Medical Monitor's approval
• Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least three months prior to Screening are allowed. No dose modification during the study will be allowed.
• Current use of fibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate
• Clinically significant history of drug sensitivity or allergy, as determined by the PI
• Uncontrolled diabetes mellitus (ie, HbA1c ≥9% or higher) 60 days prior to Day 1
• Subjects with contraindications to MRI imaging, or not being able to have the MRI performed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EDP-305 Dose 1; Subjects will take 2 tablets once a day orally for 12 weeks	Drug: EDP-305 Dose 1; Two tablets daily for 12 weeks
EXPERIMENTAL: EDP-305 Dose 2; Subjects will take 2 tablets once a day orally for 12 weeks	Drug: EDP-305 Dose 2; Two tablets daily for 12 weeks
PLACEBO_COMPARATOR: Placebo; Subjects will take 2 tablets once a day orally for 12 weeks	Drug: Placebo; Two tablets daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ALT level. Baseline refers to the average of the screening and the Day 1 values; if either the screening or Day 1 values were missing, the non-missing value was used. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12	The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the aspartate aminotransferase (AST) level and platelet count. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. The APRI score (AST to platelet ratio index) is an index comprised of biochemical values and is used to determine the degree of hepatic fibrosis. APRI is calculated from the level of AST measured in a blood test (international units per liter [IU/L]) and platelet count (10^9/L) according to the following formula: APRI = ([AST value in IU/L / upper limit of the normal range of AST] / [platelet count in 10^9/L]) × 100. In general, APRI scores range from 0 to >2.0, where scores <0.5 indicate no significant fibrosis, scores >1.5 indicate significant fibrosis, and scores >2.0 have been shown to be best correlated with the presence of cirrhosis. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Triglycerides (TG) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the TG level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Total Cholesterol at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the total cholesterol level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the LDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Adiponectin at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the adiponectin level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoA-1 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoB level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoC3 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Fasting Blood Glucose at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting glucose level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Fasting Insulin at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting insulin (in micro International units per milliliter [μIU/mL]). Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were not considered as having type 2 diabetes mellitus (T2DM) were identified as nondiabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were considered as having T2DM were identified as diabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HbA1c. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the Pharmacokinetic (PK) Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12	The Tmax was measured for EDP-305 on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Cmax of EP-022571 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Tmax of EP-022571 on Day 1 and at Week 12	The Tmax was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
AUC(Last) of EP-022571 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Cmax of EP-022572 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Tmax of EP-022572 on Day 1 and at Week 12	The Tmax was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
AUC(Last) of EP-022572 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Cmax of EP-022679 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Tmax of EP-022679 on Day 1 and at Week 12	The Tmax was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
AUC(Last) of EP-022679 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Mean Change From Baseline in Body Weight at Week 12	Body weight was measured at specific timepoints for the participants. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12	The WTH ratio is calculated as the ratio of waist to hip circumference, which was measured at specific timepoints. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc
• Collaborators: ICON Clinical Research; Triangle Biostatistics

Publications and helpful links

General Publications

• Ratziu V, Rinella ME, Neuschwander-Tetri BA, Lawitz E, Denham D, Kayali Z, Sheikh A, Kowdley KV, Desta T, Elkhashab M, DeGrauw J, Goodwin B, Ahmad A, Adda N. EDP-305 in patients with NASH: A phase II double-blind placebo-controlled dose-ranging study. J Hepatol. 2022 Mar;76(3):506-517. doi: 10.1016/j.jhep.2021.10.018. Epub 2021 Nov 3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 25, 2018
• Primary Completion (ACTUAL): June 14, 2019
• Study Completion (ACTUAL): July 10, 2019

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (ACTUAL): February 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: NASH; Non-Alcoholic Steatohepatitis (NASH)
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: EDP 305-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No