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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03421431




Registration number
NCT03421431
Ethics application status
Date submitted
29/01/2018
Date registered
5/02/2018

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis
Scientific 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)
Secondary ID [1] 0 0
EDP 305-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Alcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EDP-305 Dose 1
Treatment: Drugs - EDP-305 Dose 2
Treatment: Drugs - Placebo

Experimental: EDP-305 Dose 1 - Subjects will take 2 tablets once a day orally for 12 weeks

Experimental: EDP-305 Dose 2 - Subjects will take 2 tablets once a day orally for 12 weeks

Placebo comparator: Placebo - Subjects will take 2 tablets once a day orally for 12 weeks


Treatment: Drugs: EDP-305 Dose 1
Two tablets daily for 12 weeks

Treatment: Drugs: EDP-305 Dose 2
Two tablets daily for 12 weeks

Treatment: Drugs: Placebo
Two tablets daily for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [2] 0 0
Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12
Timepoint [2] 0 0
Baseline and Week 12
Secondary outcome [3] 0 0
Mean Change From Baseline in Triglycerides (TG) at Week 12
Timepoint [3] 0 0
Baseline and Week 12
Secondary outcome [4] 0 0
Mean Change From Baseline in Total Cholesterol at Week 12
Timepoint [4] 0 0
Baseline and Week 12
Secondary outcome [5] 0 0
Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Timepoint [5] 0 0
Baseline and Week 12
Secondary outcome [6] 0 0
Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Mean Change From Baseline in Adiponectin at Week 12
Timepoint [7] 0 0
Baseline and Week 12
Secondary outcome [8] 0 0
Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12
Timepoint [9] 0 0
Baseline and Week 12
Secondary outcome [10] 0 0
Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12
Timepoint [10] 0 0
Baseline and Week 12
Secondary outcome [11] 0 0
Mean Change From Baseline in Fasting Blood Glucose at Week 12
Timepoint [11] 0 0
Baseline and Week 12
Secondary outcome [12] 0 0
Mean Change From Baseline in Fasting Insulin at Week 12
Timepoint [12] 0 0
Baseline and Week 12
Secondary outcome [13] 0 0
Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12
Timepoint [13] 0 0
Baseline and Week 12
Secondary outcome [14] 0 0
Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12
Timepoint [14] 0 0
Baseline and Week 12
Secondary outcome [15] 0 0
Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12
Timepoint [15] 0 0
Baseline and Week 12
Secondary outcome [16] 0 0
Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12
Timepoint [16] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [17] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12
Timepoint [17] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [19] 0 0
Cmax of EP-022571 on Day 1 and at Week 12
Timepoint [19] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [20] 0 0
Tmax of EP-022571 on Day 1 and at Week 12
Timepoint [20] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [21] 0 0
AUC(Last) of EP-022571 on Day 1 and at Week 12
Timepoint [21] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [22] 0 0
Cmax of EP-022572 on Day 1 and at Week 12
Timepoint [22] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [23] 0 0
Tmax of EP-022572 on Day 1 and at Week 12
Timepoint [23] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [24] 0 0
AUC(Last) of EP-022572 on Day 1 and at Week 12
Timepoint [24] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [25] 0 0
Cmax of EP-022679 on Day 1 and at Week 12
Timepoint [25] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [26] 0 0
Tmax of EP-022679 on Day 1 and at Week 12
Timepoint [26] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [27] 0 0
AUC(Last) of EP-022679 on Day 1 and at Week 12
Timepoint [27] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary outcome [28] 0 0
Mean Change From Baseline in Body Weight at Week 12
Timepoint [28] 0 0
Baseline and Week 12
Secondary outcome [29] 0 0
Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12
Timepoint [29] 0 0
Baseline and Week 12
Secondary outcome [30] 0 0
Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12
Timepoint [30] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary outcome [31] 0 0
Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12
Timepoint [31] 0 0
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)
Secondary outcome [32] 0 0
Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12
Timepoint [32] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary outcome [33] 0 0
Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12
Timepoint [33] 0 0
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)
Secondary outcome [34] 0 0
Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12
Timepoint [34] 0 0
Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary outcome [35] 0 0
Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12
Timepoint [35] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Pessac
Country [28] 0 0
France
State/province [28] 0 0
Strasbourg
Country [29] 0 0
New Zealand
State/province [29] 0 0
Auckland
Country [30] 0 0
Puerto Rico
State/province [30] 0 0
San Juan
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Cambridgeshire
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Greater London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Nottinghamshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Enanta Pharmaceuticals, Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Triangle Biostatistics
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nathalie Adda, MD
Address 0 0
Enanta Pharmaceuticals, Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.