Non-Alcoholic SteatohepatitisPhase 2NCT03421431
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis
A Phase 2 study testing EDP-305 Dose 1 and EDP-305 Dose 2 in people with Non-Alcoholic Steatohepatitis, run by Enanta Pharmaceuticals, Inc at 82 sites in 6 countries.
Trial summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Alcoholic Steatohepatitis
- What is being tested?
- EDP-305 Dose 1 and EDP-305 Dose 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 82 sitesin 6 countries
- Study dates
- 25 Apr 2018to 10 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
Trial locations and contacts
82 sites in 6 countries.
82 sites in 6 countries
United States70 sites
Anaheim Clinical Trials
Anaheim, California, 92801
University of Michigan Health System
Ann Arbor, Michigan, 48109
Texas Clinical Research Institute
Arlington, Texas, 76012
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Texas Diabetes & Endocrinology
Austin, Texas, 78749
Mercy Medical Center
Baltimore, Maryland, 21202
Digestive Disease Associates, PA
Catonsville, Maryland, 21228
Radiant Research Incorporated
Chandler, Arizona, 85224
Carolinas Medical Center Transplant Center/Center for Liver Disease
Charlotte, North Carolina, 28204
Feinberg School of Medicine Northwestern University
Chicago, Illinois, 60611
estudy site - Chula Vista
Chula Vista, California, 91911
Sterling Research Group, Ltd.
Cincinnati, Ohio, 45219
Cleveland Clinic
Cleveland, Ohio, 44195
Peak Gastroenterology Associates
Colorado Springs, Colorado, 80907
Clinical Research Advantage, Inc. / Colorado Springs Family Practice
Colorado Springs, Colorado, 80909
Southern California Research Center
Coronado, California, 92118
Dallas Diabetes Research Center
Dallas, Texas, 75230
Avail Clinical Research, LLC
DeLand, Florida, 32720
Duke University Medical Center
Durham, North Carolina, 27710
AGA Clinical Research Associates, LLC
Egg Harbor, New Jersey, 08234
South Denver Gastroenterology,P.C.
Englewood, Colorado, 80113
Fleming Island Center for Clinical Research
Fleming Island, Florida, 32003
Fresno Clinical Research Center (FCRC)
Fresno, California, 93720
Gastroenterology Associates, PC
Gainesville, Virginia, 20155
DHAT Research Institute
Garland, Texas, 75044
Baylor College of Medicine - Advanced Liver Therapies
Houston, Texas, 77030
Carolinas Center for Liver Disease / Carolinas Health Care System
Huntersville, North Carolina, 28078
Midwest Institute For Clinical Research
Indianapolis, Indiana, 46260
Westside Center for Clinical Research
Jacksonville, Florida, 32205
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Jacksonville Center for Endoscopy - Southside ; Borland Groover Clinic
Jacksonville, Florida, 32226
Kansas City Research Institute
Kansas City, Missouri, 64131
Mayo Clinic Health System - Franciscan Healthcare
La Crosse, Wisconsin, 54601
UCSD Altman Clinical and Translational Research Institute
La Jolla, California, 92037
Precision Clinical Research, LLC.
Lauderdale Lakes, Florida, 33319
Wasatch Peak Family Practice/Radiant Research, Inc
Layton, Utah, 84041
Clinical Trials Research
Lincoln, California, 95648
Cedars-Sinai Medical Center
Los Angeles, California, 90048
National Research Institute
Los Angeles, California, 90057
Northwell Health Inc.
Manhasset, New York, 11030
Gastrointestinal Specialists Of Georgia
Marietta, Georgia, 30060
University Of Tennessee Health Science Center
Memphis, Tennessee, 38104
Central Arizona Medical Associates
Mesa, Arizona, 58206
Homestead Medical Research
Miami, Florida, 33030
Research Associates of South Florida, LLC
Miami, Florida, 33134
Florida Advanced Medical Research, Inc.
Miami, Florida, 33144
Ocean Blue Medical Research Center, Inc
Miami Springs, Florida, 33166
Catalina Research Institute, LLC
Montclair, California, 91763
Radiant Research, Inc.
Murray, Utah, 84123
Quality Medical Research, PLLC
Nashville, Tennessee, 37211
Oshsner Clinic Foundation
New Orleans, Louisiana, 70121
NYU Langone Medical Center - The Center for Musculoskeletal Care (CMC)
New York, New York, 10016
Weill Cornell Medical College
New York, New York, 10021
Bon Secours St. Mary's Hospital of Richmond, Inc
Newport News, Virginia, 23602
Clinical Neuroscience Solutions Inc.
Orlando, Florida, 32801
Advanced Gastroenterology Associates, LLC
Palm Harbor, Florida, 34684
Mayo Clinic Specialty Building
Phoenix, Arizona, 85054
University of Pittsburgh Medical Center - Center for Liver Diseases
Pittsburgh, Pennsylvania, 15213
The Gastroenterology Group, PC
Reston, Virginia, 20191
Inland Empire Liver Foundation
Rialto, California, 92377
Texas Liver Institute
San Antonio, Texas, 78215
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Radiant Research, Inc.
San Antonio, Texas, 78229
Southern California Transplantation Institute Research Foundation
San Clemente, California, 92673
Precision Research Institute
San Diego, California, 92114
Virginia Mason Medical Center
Seattle, Washington, 98101
Swedish Medical Center-Swedish Organ Transplant and Liver Center
Seattle, Washington, 98104
University of Washington / Harborview Medical Center
Seattle, Washington, 98104
WestGlen Gastrointestinal Consultants, PA
Shawnee Mission, Kansas, 66217
Saint Louis University
St Louis, Missouri, 63104
Canada4 sites
Aggarwal and Associates Limited
Brampton, Ontario, L6T OG1
Clinique de recherche Medpharmgene
Montreal, Quebec, H2K 1H2
Chronic Viral Illness Service McGill University Health Center/Royal Victoria
Montreal, Quebec, H4A 3JI
Toronto Liver Centre
Toronto, Ontario, M6H3M1
France3 sites
Hopital Pitie Salpetriere
Paris, Cedex 13
CHU de Bordeaux - GH Sud - Hoital Haut Leveque
Pessac, 33604
CHU de Strasbourg - Nouvel Hôspital Civil
Strasbourg, 67000
United Kingdom3 sites
Addenbrookes Hospital (AH)-Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
King's College Hospital NHS Foundation
London, Greater London, SE5 9RS
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: 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
- Conditions
- Non-Alcoholic Steatohepatitis
- Being tested
- EDP-305 Dose 1, EDP-305 Dose 2, Placebo
- Keywords
- NASH, Non-Alcoholic Steatohepatitis (NASH)
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EDP-305 Dose 1Drug
Two tablets daily for 12 weeks
EDP-305 Dose 2Drug
Two tablets daily for 12 weeks
PlaceboDrug
Two tablets daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| EDP-305 Dose 1 | Experimental | Subjects will take 2 tablets once a day orally for 12 weeks Receives: Drug: EDP-305 Dose 1 |
| EDP-305 Dose 2 | Experimental | Subjects will take 2 tablets once a day orally for 12 weeks Receives: Drug: EDP-305 Dose 2 |
| Placebo | Placebo comparator | Subjects will take 2 tablets once a day orally for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (35)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start25 Apr 2018
- Primary completion14 Jun 2019
- Study completion10 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enanta Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON Clinical Research, Triangle Biostatistics, LLC
- Responsible party
- Sponsor
- Investigators
- Nathalie Adda, MD, Study director, Enanta Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03421431
- Sponsor's protocol ID
- EDP 305-101
- Status last verified
- Aug 2021
- First submitted
- 29 Jan 2018
- Last updated
- 16 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34740705
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03421431
- Acronym / sponsor ID
- EDP 305-101
- Conditions
- Non-Alcoholic Steatohepatitis
- Keywords
- NASH, Non-Alcoholic Steatohepatitis (NASH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Enanta Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Collaborators
- ICON Clinical Research, Triangle Biostatistics, LLC
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- 14 Jun 2019 (actual)
- Study completion
- 10 Jul 2019 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Posted 16 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EDP-305 Dose 1 | Experimental | Drug: EDP-305 Dose 1Subjects will take 2 tablets once a day orally for 12 weeks |
| EDP-305 Dose 2 | Experimental | Drug: EDP-305 Dose 2Subjects will take 2 tablets once a day orally for 12 weeks |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will take 2 tablets once a day orally for 12 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (28 listed)
- Laboratory Screening Results:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EDP-305 Dose 1Two tablets daily for 12 weeks | Drug | EDP-305 Dose 1 |
| EDP-305 Dose 2Two tablets daily for 12 weeks | Drug | EDP-305 Dose 2 |
| PlaceboTwo tablets daily for 12 weeks | Drug | Placebo |
Primary outcome
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12
Time frame: Baseline and 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.
35 secondary outcomes
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
Time frame: Baseline and Week 12
Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Triglycerides (TG) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Total Cholesterol at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Adiponectin at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Fasting Blood Glucose at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Fasting Insulin at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12
Time frame: Baseline and Week 12
Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and Week 12
Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12
Time frame: Baseline and Week 12
Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34740705Ratziu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathalie Adda, MD study director
Enanta Pharmaceuticals, Inc
82 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EDP-305 Dose 1 and EDP-305 Dose 2 in people with Non-Alcoholic Steatohepatitis, run by Enanta Pharmaceuticals, Inc at 82 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 82 sites in United States, Canada, France, United Kingdom, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03421431, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.