Clinical trial NCT04008004: A Study of EDP-514 in Healthy Subjects (Part 1) and Patients With Chronic Hepatitis B Virus Infection (Part 2)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic HBV Infection
Keywords: "First-in-Human"
Single Ascending Dose
Multiple Ascending Dose
hepatitis B virus
HBV
Lead sponsor: Enanta Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Pharmaceutical Research Associates
First posted: 2019-07-05
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety measured by adverse events
timeFrame: Up to 8 Days in HV SAD Cohorts
measure: Safety measured by adverse events
timeFrame: Up to 21 Days in HV MAD Cohorts
measure: Safety measured by adverse events
timeFrame: Up to 56 Days in HBV MAD Cohorts
Secondary outcomes:
measure: Cmax of EDP-514
timeFrame: Up to 6 Days in HV SAD Cohorts
measure: AUC of EDP-514
timeFrame: Up to 6 Days in HV SAD Cohorts
measure: Cmax of EDP-514
timeFrame: Up to 18 Days in HV MAD Cohorts
measure: AUC of EDP-514
timeFrame: Up to 18 Days in HV MAD Cohorts
measure: Cmax of EDP-514
timeFrame: Up to 28 Days in HBV MAD Cohorts
measure: AUC of EDP-514
timeFrame: Up to 28 Days in HBV MAD Cohorts
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California GI and Liver Centers
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Diego
country: United States
facility: Tuan Nguyen Md Gastroenterology & Hepatology (Tuan Nguyen, M.D., Inc.)
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Lenexa
country: United States
facility: Pharmaceutical Research Associates, Inc.
state: Kansas
city: Catonsville
country: United States
facility: Digestive Disease Associates - Catonsville
state: Maryland
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Houston
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: The Texas Liver Institute
state: Texas
city: Seattle
country: United States
facility: Swedish Organ Transplant and Liver Center
state: Washington
city: Calgary
country: Canada
facility: University Of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Gastroenterology Institute of Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Enanta Pharmaceuticals, Inc
name: Enanta Pharmaceuticals, Inc
role: STUDY_DIRECTOR
References: