Clinical trial NCT04971512: 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.
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-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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hepatitis B Virus Infection
Keywords: First-in-Human
Single Ascending Dose
Multiple Ascending Dose
Hepatitis B virus
HBV
Lead sponsor: Enanta Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2021-07-21
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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 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.


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.

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

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 70 Days in NUC-suppressed CHB MAD Cohorts
measure: Safety measured by adverse events
timeFrame: Up to 98 Days in Viremic CHB MAD Cohorts
Secondary outcomes:
measure: Cmax of EDP-721
timeFrame: Up to 6 Days in HV SAD Cohorts
measure: AUC of EDP-721
timeFrame: Up to 6 Days in HV SAD Cohorts
measure: Cmax of EDP-721
timeFrame: Up to 18 Days in HV MAD Cohorts
measure: AUC of EDP-721
timeFrame: Up to 18 Days in HV MAD Cohorts
measure: Cmax of EDP-721 alone and in combination with EDP-514
timeFrame: Up to 28 Days in All CHB MAD Cohorts
measure: AUC of EDP-721 alone and in combination with EDP-514
timeFrame: Up to 28 Days in All CHB MAD Cohorts
measure: Cmax of EDP-514 in combination with EDP-721
timeFrame: Up to 28 Days in All CHB MAD Cohorts
measure: AUC of EDP-514 in combination with EDP-721
timeFrame: Up to 28 Days in All CHB MAD Cohorts
measure: Change from baseline in HBV DNA Viral Load Assay
timeFrame: Through Day 28 in All CHB MAD Cohorts
measure: Change from baseline in quantitative HBsAg
timeFrame: Through Day 28 in All CHB MAD Cohorts
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research Ltd
Study officials:
affiliation: Enanta Pharmaceuticals, Inc
name: Enanta Pharmaceuticals, Inc
role: STUDY_DIRECTOR
References: