A 2 PART STUDY EVALUATING EDP-721 IN HEALTHY SUBJECTS AND EDP-721 IN COMBINATION WITH EDP-514 IN PATIENTS WITH CHRONIC HEPATITIS B VIRUS INFECTION.

Study Overview
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Brief Summary
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Part 1 is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EDP-721 in healthy subjects. Part 2 is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of EDP-721 in combination with EDP-514 in patients with chronic hepatitis B virus infection.

Official Title
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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-721 in Healthy Subjects (Part 1) and the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of EDP-721 in Combination With EDP-514 in Patients With Chronic Hepatitis B Virus Infection (Part 2)

Conditions
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Chronic Hepatitis B Virus Infection

Intervention / Treatment
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* Drug: EDP-721
* Drug: Placebo (Part 1)
* Drug: EDP-721 (Part 2)
* Drug: Placebo (Part 2)
* Drug: EDP-514
* Drug: Placebo (Part 2)


Participation Criteria
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Eligibility Criteria
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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. Part 2 (CHB Population) Inclusion Criteria (Nuc-Suppressed CHB Population) 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 HBsAg detectable in serum/plasma at Screening and in the most recent HBsAg serum/plasma testing at least 6 months previously. 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 Inclusion Criteria (Viremic CHB Population): 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 HBsAg detectable in serum/plasma at Screening and in the most recent HBsAg serum/plasma testing at least 6 months previously. HBV DNA levels: For subjects who are HBeAg positive at Screening, a Screening HBV DNA level in serum/plasma that is ≥20,000 IU/ml, or For subjects who are HBeAg negative at Screening, a Screening HBV DNA level in serum/plasma that is ≥2,000 IU/mL, and For all subjects, no HBV DNA serum/plasma test values <1,000 IU/ml over the previous 12 months (using an approved test) CHB subjects must not have been on prescribed anti-HBV treatment, specifically pegIFN and/or NUC therapy for at least 12 months prior to Screening Exclusion Criteria (Nuc-Suppressed and Viremic CHB Population): 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
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EDP-721 HV SAD Cohorts<br>EDP-721 Dose 1, Dose 2, Dose 3 and Dose 4, in one single administration | Drug: EDP-721<br>* Oral administration (Part 1)<br>|
| Experimental: EDP-721 HV MAD Cohorts<br>EDP-721 Dose 1, Dose 2 and Dose 3, once daily for 14 days | Drug: EDP-721<br>* Oral administration (Part 1)<br>|
| Placebo Comparator: EDP-721 HV SAD Placebo Cohort<br>Matching placebo, in one single administration | Drug: Placebo (Part 1)<br>* Placebo to match EDP-721, oral administration (Part 1)<br>|
| Placebo Comparator: EDP-721 HV MAD Placebo Cohort<br>Matching placebo, once daily for 14 days | Drug: Placebo (Part 1)<br>* Placebo to match EDP-721, oral administration (Part 1)<br>|
| Experimental: EDP-721+ EDP-514 HBV MAD Cohorts<br>EDP-721 once daily for 14 days followed by EDP-721+EDP-514 once daily for 28 days | Drug: EDP-721 (Part 2)<br>* Oral administration (Part 2)<br>Drug: EDP-514<br>* Oral administration<br>|
| Placebo Comparator: EDP-721+ EDP-514 HBV MAD Placebo Cohorts<br>Matching placebo once daily for 42 days | Drug: Placebo (Part 2)<br>* Placebo to match EDP-721 (Part 2)<br>Drug: Placebo (Part 2)<br>* Placebo to match EDP-514<br>|

What is the study measuring?
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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 70 Days in NUC-suppressed CHB MAD Cohorts | 
| Safety measured by adverse events |  | Up to 98 Days in Viremic CHB MAD Cohorts | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of EDP-721 |  | Up to 6 Days in HV SAD Cohorts | 
| AUC of EDP-721 |  | Up to 6 Days in HV SAD Cohorts | 
| Cmax of EDP-721 |  | Up to 18 Days in HV MAD Cohorts | 
| AUC of EDP-721 |  | Up to 18 Days in HV MAD Cohorts | 
| Cmax of EDP-721 alone and in combination with EDP-514 |  | Up to 28 Days in All CHB MAD Cohorts | 
| AUC of EDP-721 alone and in combination with EDP-514 |  | Up to 28 Days in All CHB MAD Cohorts | 
| Cmax of EDP-514 in combination with EDP-721 |  | Up to 28 Days in All CHB MAD Cohorts | 
| AUC of EDP-514 in combination with EDP-721 |  | Up to 28 Days in All CHB MAD Cohorts | 
| Change from baseline in HBV DNA Viral Load Assay |  | Through Day 28 in All CHB MAD Cohorts | 
| Change from baseline in quantitative HBsAg |  | Through Day 28 in All CHB MAD Cohorts | 

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