A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir

• ClinicalTrials.gov Identifier: NCT04365933
• Recruitment Status: Recruiting
• First Posted: April 28, 2020
• Last Update Posted: September 25, 2020
• Sponsor: Enyo Pharma
• Information provided by (Responsible Party): Enyo Pharma

Tracking Information

• First Submitted Date: April 23, 2020
• First Posted Date: April 28, 2020
• Last Update Posted Date: September 25, 2020
• Actual Study Start Date: May 25, 2020
• Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2020)

• Number of Treatment-emergent adverse events [ Time Frame: 16 weeks ]
  Number of Treatment-emergent adverse events including serious adverse events
• Measurement of HBsAg decline [ Time Frame: 16 weeks ]
  Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 27, 2020)

• Measurement of HBsAg decline [ Time Frame: 40 weeks ]
  Measurement of HBsAg decline (Δ log10)
• Measurement of HBV-DNA decline [ Time Frame: 40 weeks ]
  Measurement of HBV-DNA decline (Δ log10)
• Measurement of HBV-pgRNA decline [ Time Frame: 40 weeks ]
  Measurement of HBV-pgRNA decline (Δ log10)
• Measurement of HBcrAg decline [ Time Frame: 40 weeks ]
  Measurement of HBcrAg decline (Δ log10)
• Concentration of EYP001a - Pharmacokinetic [ Time Frame: 20 weeks ]
  Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry
• Concentration of C4 - Pharmacodynamic biomarker [ Time Frame: 40 weeks ]
  Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)
• Concentration of FGF19 - Pharmacodynamic biomarker [ Time Frame: 40 weeks ]
  Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)
• Concentration of Bile Acids - Pharmacodynamic biomarker [ Time Frame: 40 weeks ]
  Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir
• Official Title: A Phase 2a Open-label Study of the Oral Farnesoid X Receptor (FXR) Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B (CHB) Patients in Combination With Pegylated Interferon alpha2a (Peg-IFN) Alone and With Entecavir (ETV)
• Brief Summary: This is a multi centre, two parallel arm, randomized, open-label, Phase 2a experimental study of oral Farnesoid X Receptor (FXR) modulator EYP001a to assess its safety and anti-viral effect when administered to non-treated (treatment naive or off treatment) chronic Hepatitis B (CHB) patients in combination with entecavir (ETV) and pegylated interferon alpha2a (peg-IFN). An experimental treatment period of 16 weeks will be followed by a 24 week maintenance period with ETV standard of care (SoC).

Detailed Description

In total 30 eligible patients will be enrolled and randomized at approximately 7 study sites.

Patients will be randomized prior to study drug (EYP001a, ETV and peg-IFN) administration on Day 1 in the ratio of 1:1 into 2 treatment arms:

• Arm 1: EYP001a QD + ETV 0.5 mg QD + peg-IFN 180 µg QW (± 3 days) (15 patients)
• Arm 2: EYP001a QD + peg-IFN 180 µg QW (± 3 days) (15 patients)

Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 30 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: 4 weeks (30 days)
• 16 weeks treatment period
• 24 weeks maintenance period. During maintenance period patients are kept on ETV until the end of the trial at Week 40.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis B, Chronic

Intervention

• Drug: EYP001a
  Oral tablets
• Drug: Entecavir
  Oral tablets
• Drug: Pegylated interferon alpha2a
  Subcutaneous

Study Arms

• Experimental: Arm 1
  EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN 180 µg QW
  Interventions:

  • Drug: EYP001a
  • Drug: Entecavir
  • Drug: Pegylated interferon alpha2a
• Experimental: Arm 2
  EYP001a Dose A QD + peg-IFN 180 µg QW
  Interventions:

  • Drug: EYP001a
  • Drug: Pegylated interferon alpha2a

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 27, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2021
• Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has given voluntary written informed consent before performance of any study related procedure.
• Are treatment naive or without HBV treatment for at least 60 days or 5 times the elimination half-life, whichever is longer.

• Patient has CHB:

  1. HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
  2. HBsAg ≥ 2.5 log10 IU/mL.
• Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
• Patient 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.

Exclusion Criteria:

• Is an employee of a clinical research organization, vendor, or Sponsor involved with this study.
• Has known hepatocellular carcinoma or pancreaticobiliary disease.
• Neutropenia (defined by two confirmed values during Screening period of < 1500/μL).
• Has Gilbert syndrome.
• Shows evidence of worsening liver tests, defined as either a confirmed (2 assessments at least 3 days apart) increase > 2 ULN ALT or AST or an increase of > 1.5 × baseline 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 F4 stage with a vibration controlled transient elastography (VCTE) > 11.7 kPa leads to exclusion
• Has known history of alcohol abuse or daily heavy alcohol consumption

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

  1. ALT > 2 × ULN, AST > 2 × ULN
  2. INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
  3. Platelet count < 100 G/L
  4. Estimated glomerular filtration rate < 60 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
  5. Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Javiera Kaiser; +61 3 9341 1900; Javiera.Kaiser@novotech-cro.com

• Listed Location Countries: Korea, Republic of, Taiwan

Administrative Information

• NCT Number: NCT04365933
• Other Study ID Numbers: EYP001-203
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Enyo Pharma
• Study Sponsor: Enyo Pharma
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Enyo Pharma
• Verification Date: September 2020