A Study of EDP-514 in Healthy Subjects (Part 1) and Patients With Chronic Hepatitis B Virus Infection (Part 2)

A Phase 1a/1b Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of EDP 514 in Healthy Subjects (Part 1), and Antiviral Activity in Nucleos(t)Ide Reverse Transcriptase Inhibitor (NUC)-Suppressed Patients With Chronic Hepatitis B Virus Infection (Part 2)

Part 1 is a randomized, double-blind, placebo-controlled study. It will assess the safety, tolerability, and pharmacokinetics of single and multiple orally administered doses of EDP-514 in healthy adult subjects.

Part 2 is randomized, double -blind, placebo-controlled study including subjects with Hepatitis B Virus. It will assess the safety, tolerability, pharmacokinetics and antiviral activity of 28 Days of orally administered doses of EDP-514 in nucleos(t)ide reverse transcriptase inhibitor (NUC)-Suppressed Patients with Chronic Hepatitis B Virus Infection

Study Overview

• Status: Completed
• Conditions: Chronic HBV Infection
• Intervention / Treatment: Drug: EDP-514; Drug: Placebo

Detailed Description

Part 1 consists of two phases planned in healthy subjects:

The first phase assesses single ascending doses for EDP-514 (active drug or placebo) in healthy subjects. A "fasted" and "fed" two-part cohort will also assess food effect.

The second phase assesses multiple ascending doses (active drug or placebo) for 14 days in healthy subjects.

Each cohort within each phase will enroll a total of 8 subjects who will be randomized to receive EDP-514 or placebo. The cohort assessing food effect will enroll 10 subjects randomized to receive EDP-514 or placebo.

Part 2 assesses multiple ascending doses EDP-514 (active drug or placebo) for 28 days in nucleos(t)ide reverse transcriptase inhibitor (NUC)-Suppressed Patients with Chronic Hepatitis B Virus Infection.

Each cohort in Part 2 will enroll a total of 8 subjects who will be randomized to receive EDP-514 or placebo.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Gastroenterology Institute of Research Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal
• United States
  • California
    • Coronado, California, United States, 92118
      • Southern California GI and Liver Centers
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • San Diego, California, United States, 92105
      • Tuan Nguyen Md Gastroenterology & Hepatology (Tuan Nguyen, M.D., Inc.)
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Pharmaceutical Research Associates, Inc.
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates - Catonsville
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Texas
    • Houston, Texas, United States, 77030
      • American Research Corporation
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Organ Transplant and Liver Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Part 1 (HV Population):

Inclusion Criteria:

• An informed consent document signed and dated by the subject.
• Healthy male and female subjects of any ethnic origin between the ages of 18 and 65 years, inclusive.

Exclusion Criteria:

• Clinically relevant evidence or history of illness or disease.
• Pregnant or nursing females.
• History of febrile illness within 7 days prior to the first dose of study drug or subjects with evidence of active infection.
• A positive urine drug screen at screening or Day -1.
• Current tobacco smokers or use of tobacco within 3 months prior to screening.
• Any condition possibly affecting drug absorption (e.g., gastrectomy, cholecystectomy).
• History of regular alcohol consumption.
• Receipt of any vaccine, an investigational agent or biological product within 28 days or 5 times the t½, whichever one is longer, prior to first dose. This includes agents administered during clinical trial participation.

Part 2 (HBV Population):

Inclusion Criteria:

• An informed consent document signed and dated by the subject.
• Healthy male and female subjects of any ethnic origin between the ages of 18 and 70 years, inclusive

• HBV DNA levels:

  • A Screening HBV DNA level in serum/plasma that is <LLOQ and
  • No HBV DNA serum/plasma test values ≥LLOQ over the previous 12 months (using an approved test)
• CHB subjects must have been on their prescribed HBV NUC treatment with no change in regimen for 12 months prior to Screening

Exclusion Criteria:

• A documented prior diagnosis of cirrhosis
• Pregnant or nursing females
• Coinfection with human immunodeficiency virus (HIV), HCV, HDV, HAV, or HEV
• Chronic liver disease of a non-HBV etiology; coexisting liver or biliary diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP-514 HV SAD Cohorts; EDP-514 Dose 1, Dose 2, Dose 3, Dose 4, Dose 5 and Dose 6 orally, once daily in one single administration	Drug: EDP-514; Oral Capsule; Subjects will receive either a single dose of EDP-514 on Day 1 only (SAD HV), once daily dosing of EDP-514 starting on Day 1 through Day 14 (MAD HV) or once daily dosing of EDP-514 starting on Day 1 through Day 28 (MAD HBV).
Experimental: EDP-514 HV MAD Cohorts; EDP-514 Dose 1, Dose 2 and Dose 3 orally, once daily for 14 days	Drug: EDP-514; Oral Capsule; Subjects will receive either a single dose of EDP-514 on Day 1 only (SAD HV), once daily dosing of EDP-514 starting on Day 1 through Day 14 (MAD HV) or once daily dosing of EDP-514 starting on Day 1 through Day 28 (MAD HBV).
Placebo Comparator: EDP-514 HV SAD Placebo Cohort; Matching placebo, orally, once daily in one single administration	Drug: Placebo; Placebo to match EDP-514
Placebo Comparator: EDP-514 HV MAD Placebo Cohort; Matching placebo, orally, once daily for 14 days	Drug: Placebo; Placebo to match EDP-514
Experimental: EDP-514 HBV MAD Cohorts; EDP-514 Dose 1, Dose 2 and Dose 3 orally, once daily for 28 days	Drug: EDP-514; Oral Capsule; Subjects will receive either a single dose of EDP-514 on Day 1 only (SAD HV), once daily dosing of EDP-514 starting on Day 1 through Day 14 (MAD HV) or once daily dosing of EDP-514 starting on Day 1 through Day 28 (MAD HBV).
Placebo Comparator: EDP-514 HBV MAD Placebo Cohort; Matching placebo, orally, once daily for 28 days	Drug: Placebo; Placebo to match EDP-514

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety measured by adverse events	Up to 8 Days in HV SAD Cohorts
Safety measured by adverse events	Up to 21 Days in HV MAD Cohorts
Safety measured by adverse events	Up to 56 Days in HBV MAD Cohorts

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax of EDP-514	Up to 6 Days in HV SAD Cohorts
AUC of EDP-514	Up to 6 Days in HV SAD Cohorts
Cmax of EDP-514	Up to 18 Days in HV MAD Cohorts
AUC of EDP-514	Up to 18 Days in HV MAD Cohorts
Cmax of EDP-514	Up to 28 Days in HBV MAD Cohorts
AUC of EDP-514	Up to 28 Days in HBV MAD Cohorts

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc
• Collaborators: Pharmaceutical Research Associates

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Actual): July 14, 2021
• Study Completion (Actual): July 14, 2021

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 6, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: HBV; hepatitis B virus; Single Ascending Dose; Multiple Ascending Dose; "First-in-Human"
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Blood-Borne Infections; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Virus Diseases; Hepatitis B, Chronic; Herpesviridae Infections
• Other Study ID Numbers: EDP 514-001

Drug and device information, study documents

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