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.

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)

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B Virus Infection
• Intervention / Treatment: Drug: EDP-721; Drug: Placebo (Part 1); Drug: EDP-721 (Part 2); Drug: EDP-514; Drug: Placebo (Part 2); Drug: Placebo (Part 2)

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• 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.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Enanta Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): December 20, 2021

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: First-in-Human; HBV; Hepatitis B virus; Single Ascending Dose; Multiple Ascending Dose
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Hepatitis, Chronic; Herpesviridae Infections
• Other Study ID Numbers: EDP 721-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes