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

NCT ID: NCT03421431

Last Updated: 2021-09-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

134 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-25

Study Completion Date

2019-07-10

Brief Summary

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

Detailed Description

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Conditions

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Non-Alcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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EDP-305 Dose 1

Subjects will take 2 tablets once a day orally for 12 weeks

Group Type EXPERIMENTAL

EDP-305 Dose 1

Intervention Type DRUG

Two tablets daily for 12 weeks

EDP-305 Dose 2

Subjects will take 2 tablets once a day orally for 12 weeks

Group Type EXPERIMENTAL

EDP-305 Dose 2

Intervention Type DRUG

Two tablets daily for 12 weeks

Placebo

Subjects will take 2 tablets once a day orally for 12 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Two tablets daily for 12 weeks

Interventions

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EDP-305 Dose 1

Two tablets daily for 12 weeks

Intervention Type DRUG

EDP-305 Dose 2

Two tablets daily for 12 weeks

Intervention Type DRUG

Placebo

Two tablets daily for 12 weeks

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ICON Clinical Research

INDUSTRY

Sponsor Role collaborator

Triangle Biostatistics, LLC

INDUSTRY

Sponsor Role collaborator

Enanta Pharmaceuticals, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nathalie Adda, MD

Role: STUDY_DIRECTOR

Enanta Pharmaceuticals, Inc

Locations

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Radiant Research Incorporated

Chandler, Arizona, United States

Site Status

Central Arizona Medical Associates

Mesa, Arizona, United States

Site Status

Mayo Clinic Specialty Building

Phoenix, Arizona, United States

Site Status

Anaheim Clinical Trials

Anaheim, California, United States

Site Status

estudy site - Chula Vista

Chula Vista, California, United States

Site Status

Southern California Research Center

Coronado, California, United States

Site Status

Fresno Clinical Research Center (FCRC)

Fresno, California, United States

Site Status

UCSD Altman Clinical and Translational Research Institute

La Jolla, California, United States

Site Status

Clinical Trials Research

Lincoln, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

National Research Institute

Los Angeles, California, United States

Site Status

Catalina Research Institute, LLC

Montclair, California, United States

Site Status

Inland Empire Liver Foundation

Rialto, California, United States

Site Status

Southern California Transplantation Institute Research Foundation

San Clemente, California, United States

Site Status

Precision Research Institute

San Diego, California, United States

Site Status

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

Site Status

Clinical Research Advantage, Inc. / Colorado Springs Family Practice

Colorado Springs, Colorado, United States

Site Status

South Denver Gastroenterology,P.C.

Englewood, Colorado, United States

Site Status

Avail Clinical Research, LLC

DeLand, Florida, United States

Site Status

Fleming Island Center for Clinical Research

Fleming Island, Florida, United States

Site Status

Westside Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Jacksonville Center for Endoscopy - Southside ; Borland Groover Clinic

Jacksonville, Florida, United States

Site Status

Precision Clinical Research, LLC.

Lauderdale Lakes, Florida, United States

Site Status

Homestead Medical Research

Miami, Florida, United States

Site Status

Research Associates of South Florida, LLC

Miami, Florida, United States

Site Status

Florida Advanced Medical Research, Inc.

Miami, Florida, United States

Site Status

Ocean Blue Medical Research Center, Inc

Miami Springs, Florida, United States

Site Status

Clinical Neuroscience Solutions Inc.

Orlando, Florida, United States

Site Status

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Gastrointestinal Specialists Of Georgia

Marietta, Georgia, United States

Site Status

Feinberg School of Medicine Northwestern University

Chicago, Illinois, United States

Site Status

Midwest Institute For Clinical Research

Indianapolis, Indiana, United States

Site Status

WestGlen Gastrointestinal Consultants, PA

Shawnee Mission, Kansas, United States

Site Status

Oshsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Digestive Disease Associates, PA

Catonsville, Maryland, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Kansas City Research Institute

Kansas City, Missouri, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

AGA Clinical Research Associates, LLC

Egg Harbor, New Jersey, United States

Site Status

Northwell Health Inc.

Manhasset, New York, United States

Site Status

NYU Langone Medical Center - The Center for Musculoskeletal Care (CMC)

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Carolinas Medical Center Transplant Center/Center for Liver Disease

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Carolinas Center for Liver Disease / Carolinas Health Care System

Huntersville, North Carolina, United States

Site Status

Sterling Research Group, Ltd.

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

University of Pittsburgh Medical Center - Center for Liver Diseases

Pittsburgh, Pennsylvania, United States

Site Status

University Of Tennessee Health Science Center

Memphis, Tennessee, United States

Site Status

Quality Medical Research, PLLC

Nashville, Tennessee, United States

Site Status

Texas Clinical Research Institute

Arlington, Texas, United States

Site Status

Texas Diabetes & Endocrinology

Austin, Texas, United States

Site Status

Dallas Diabetes Research Center

Dallas, Texas, United States

Site Status

DHAT Research Institute

Garland, Texas, United States

Site Status

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

Site Status

Texas Liver Institute

San Antonio, Texas, United States

Site Status

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

Site Status

Radiant Research, Inc.

San Antonio, Texas, United States

Site Status

Wasatch Peak Family Practice/Radiant Research, Inc

Layton, Utah, United States

Site Status

Radiant Research, Inc.

Murray, Utah, United States

Site Status

Gastroenterology Associates, PC

Gainesville, Virginia, United States

Site Status

Bon Secours St. Mary's Hospital of Richmond, Inc

Newport News, Virginia, United States

Site Status

The Gastroenterology Group, PC

Reston, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Swedish Medical Center-Swedish Organ Transplant and Liver Center

Seattle, Washington, United States

Site Status

University of Washington / Harborview Medical Center

Seattle, Washington, United States

Site Status

Mayo Clinic Health System - Franciscan Healthcare

La Crosse, Wisconsin, United States

Site Status

Aggarwal and Associates Limited

Brampton, Ontario, Canada

Site Status

Toronto Liver Centre

Toronto, Ontario, Canada

Site Status

Clinique de recherche Medpharmgene

Montreal, Quebec, Canada

Site Status

Chronic Viral Illness Service McGill University Health Center/Royal Victoria

Montreal, Quebec, Canada

Site Status

Hopital Pitie Salpetriere

Paris, , France

Site Status

CHU de Bordeaux - GH Sud - Hoital Haut Leveque

Pessac, , France

Site Status

CHU de Strasbourg - Nouvel Hôspital Civil

Strasbourg, , France

Site Status

Auckland Clinical Studies Limited

Auckland, , New Zealand

Site Status

Latin Clinical Trial Center

San Juan, , Puerto Rico

Site Status

Addenbrookes Hospital (AH)-Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, United Kingdom

Site Status

King's College Hospital NHS Foundation

London, Greater London, United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, United Kingdom

Site Status

Countries

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United States Canada France New Zealand Puerto Rico United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34740705 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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EDP 305-101

Identifier Type: -

Identifier Source: org_study_id

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