Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD)

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study of Oral FXR Modulator EYP001a Combined With Nucleos(t)Ide Analogues (NA) in Virologically Suppressed Chronic Hepatitis B Patients to Improve Functional Cure Rates

This is a prospective, multi-centre, randomized, double-blind, placebo-controlled, Phase 2a experimental study of oral FXR modulator EYP001a/placebo combined with NAs in virologically suppressed CHB patients to improve functional cure rates.

Study Overview

• Status: Terminated
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: EYP001a; Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil)

Detailed Description

A total of 49 eligible patients will be enrolled and randomized at approximately 14 study sites. Patients will be randomized prior to study drug (EYP001a or placebo and NA) administration on Day 1 in the ratio of 3:1 into 2 arms:

• Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)
• Control Arm: Placebo + NA daily (12 patients)

The maximum total engagement duration for eligible patients in this study is up to 370 days: 90 days screening, 112 days (16 weeks) treatment period and 168 days (24 weeks) follow-up.

Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 90 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify for study drug administration on Day 1.

The visits during the study are planned as below:

• Screening visit: 12 weeks (90 days)
• 16 weeks treatment period:
• Treatment Visit 1 (Week 1 [Day 1])
• Treatment Visit 2 (Week 2 [Day 14 ±3 days])
• Treatment Visit 3 (Week 4 [Day 28 ±3 days])
• Treatment Visit 4 (Week 6 [Day 42 ±3 days])
• Treatment Visit 5 (Week 8 [Day 56 ±3 days])
• Treatment Visit 6 (Week 10 [Day 70 ± 3 days])
• Treatment Visit 7 (Week 12 [Day 84 ± 3 days])
• Treatment Visit 8 (Week 14 [Day 98 ± 3 days])
• Treatment Visit 9 (Week 16 [Day 112±3 days])
• 24 weeks safety follow-up period:
• Follow-up Visit 1 (Week 20 [Day 140 ±7 days])
• Follow-up Visit 2 (Week 28 [Day 196 ±7 days])
• Follow-up Visit 3 (Week 40 [Day 280 ±7 days]) Note: during follow-up patients are kept on NA until the end of the trial: Week 40 (consolidation Phase).

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • ENYO PHARMA Investigative site AU02
  • Melbourne, Australia
    • ENYO PHARMA Investigative site AU01
  • Melbourne, Australia
    • ENYO PHARMA Investigative site AU03
  • Melbourne, Australia
    • ENYO PHARMA Investigative site AU04
• Hong Kong
  • Hong Kong, Hong Kong
    • ENYO PHARMA Investigative site HK01
• Korea, Republic of
  • Pusan, Korea, Republic of
    • ENYO PHARMA Investigative site KR04
  • Pusan, Korea, Republic of
    • ENYO PHARMA Investigative site KR07
  • Seongnam, Korea, Republic of
    • ENYO PHARMA Investigative site KR05
  • Seoul, Korea, Republic of
    • ENYO PHARMA Investigative site KR01
  • Seoul, Korea, Republic of
    • ENYO PHARMA Investigative site KR02
  • Seoul, Korea, Republic of
    • ENYO PHARMA Investigative site KR03
  • Séoul, Korea, Republic of
    • ENYO PHARMA Investigative site KR06
• Poland
  • Białystok, Poland
    • ENYO PHARMA Investigative site PL01
  • Kielce, Poland
    • ENYO PHARMA Investigative site PL06
  • Lublin, Poland
    • ENYO PHARMA Investigative site PL02
  • Warszawa, Poland
    • ENYO PHARMA Investigative site PL03
  • Zawiercie, Poland
    • ENYO PHARMA Investigative site PL04
  • Łódź, Poland
    • ENYO PHARMA Investigative site PL05

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Are on stable NA therapy at least 12 months from the screening date (ETV or TDF)
• Has virally suppressed CHB:

HBV DNA <LLOQ and serum HBsAg >100 IU/mL

• Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
• Is not of childbearing potential or, if of childbearing potential, is not pregnant as confirmed by a negative serum human chorionic gonadotropin test at screening and is not planning a pregnancy during the course of the study.

Main Exclusion Criteria:

• Is an employee of a contract research organization (CRO), vendor, or Sponsor involved with this study.
• Has known hepatocellular carcinoma or pancreaticobiliary disease.
• Neutropenia (defined by two confirmed values within screening period of <1500/μL).
• Has Gilbert syndrome.
• Shows evidence of worsening liver function, defined as either a confirmed (two assessments at least 3 days apart) increase >2 ULN ALT or AST or an increase of >1.5 × first assessed value of TBL or associated with clinical signs or symptoms of liver impairment.
• Has known or suspected non-CHB liver disease
• History of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of oesophageal varices.
• Probable or possible F3 stage with a vibration controlled transient elastography (VCTE). Patients with normal baseline ALT and VCTE >8.8 kPa are excluded. Patients with baseline ALT >ULN (but <2ULN per EC5) and who have VCTE >10.5 kPa at baseline are excluded 11.
• Has known history of alcohol abuse or daily heavy alcohol consumption
• Has clinically relevant immunosuppression, including, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Has used anti-HBV medications other than NAs within 90 days prior to screening.

• Has any of the following exclusionary laboratory results at screening:

  1. Estimated glomerular filtration rate <60 mL/min/1.73 m2 (the Modification of Diet in Renal Disease formula).
  2. Thyroid-stimulating hormone >1.5× ULN or abnormal free triiodothyronine or free thyroxine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)	Drug: EYP001a; Oral tablets; Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil); Oral tablets
Placebo Comparator: Control Arm; Control Arm: Placebo + NA daily (12 patients)	Drug: Placebo; Oral tablets; Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil); Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment	Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment	LS mean at week 16 (Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, and Week 16)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Failure Rate	Virologic failure rate (breakthrough)2 of HBV-DNA (% patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ3) assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up period	40 weeks

Collaborators and Investigators

• Sponsor: Enyo Pharma
• Collaborators: Parexel; Novotech (Australia) Pty Limited; Synteract, Inc.; Eurofins
• Investigators: Principal Investigator: ENYO PHARMA Investigative site KR04, Pusan, South Korea; Principal Investigator: ENYO PHARMA Investigative site KR03, Séoul, South Korea; Principal Investigator: ENYO PHARMA Investigative site KR02, Séoul, South Korea; Principal Investigator: ENYO PHARMA Investigative site KR01, Séoul, South Korea; Principal Investigator: ENYO PHARMA Investigative site PL06, Kielce, Poland; Principal Investigator: ENYO PHARMA Investigative site PL05, Łódź, Poland; Principal Investigator: ENYO PHARMA Investigative site PL04, Zawiercie, Poland; Principal Investigator: ENYO PHARMA Investigative site PL03, Warszawa, Poland; Principal Investigator: ENYO PHARMA Investigative site PL02, Lublin, Poland; Principal Investigator: ENYO PHARMA Investigative site PL01, Białystok, Poland; Principal Investigator: ENYO PHARMA Investigative site AU04, Melbourne, Australia; Principal Investigator: ENYO PHARMA Investigative site AU03, Melbourne, Australia; Principal Investigator: ENYO PHARMA Investigative site AU02, Brisbane, Australia; Principal Investigator: ENYO PHARMA Investigative site AU01, Melbourne, Australia; Principal Investigator: ENYO PHARMA Investigative site HK01, Hong Kong, Hong Kong; Principal Investigator: ENYO PHARMA Investigative site KR05, Seongnam, South Korea; Principal Investigator: ENYO PHARMA Investigative site KR06, Séoul, South Korea; Principal Investigator: ENYO PHARMA Investigative site KR07, Pusan, South Korea

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2020
• Primary Completion (Actual): June 17, 2021
• Study Completion (Actual): November 25, 2021

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: EYP001-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No