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

Study Overview
=================
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.

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)

Conditions
-----------------
Chronic HBV Infection

Intervention / Treatment
-----------------
* Drug: EDP-514
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EDP-514 HV SAD Cohorts<br>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<br>* 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).<br>|
| Experimental: EDP-514 HV MAD Cohorts<br>EDP-514 Dose 1, Dose 2 and Dose 3 orally, once daily for 14 days | Drug: EDP-514<br>* 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).<br>|
| Placebo Comparator: EDP-514 HV SAD Placebo Cohort<br>Matching placebo, orally, once daily in one single administration | Drug: Placebo<br>* Placebo to match EDP-514<br>|
| Placebo Comparator: EDP-514 HV MAD Placebo Cohort<br>Matching placebo, orally, once daily for 14 days | Drug: Placebo<br>* Placebo to match EDP-514<br>|
| Experimental: EDP-514 HBV MAD Cohorts<br>EDP-514 Dose 1, Dose 2 and Dose 3 orally, once daily for 28 days | Drug: EDP-514<br>* 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).<br>|
| Placebo Comparator: EDP-514 HBV MAD Placebo Cohort<br>Matching placebo, orally, once daily for 28 days | Drug: Placebo<br>* Placebo to match EDP-514<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
First-in-Human, Single Ascending Dose, Multiple Ascending Dose, hepatitis B virus, HBV