Clinical trial NCT04365933: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Enyo Pharma
Sponsor class: INDUSTRY
First posted: 2020-04-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
* Arm 2: EYP001a QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)

Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 37 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: 5 weeks (37 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.

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 \< 50 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.

Primary outcomes:
measure: Number of Treatment-emergent adverse events
timeFrame: 16 weeks
measure: Measurement of HBsAg decline
timeFrame: 16 weeks
Secondary outcomes:
measure: Measurement of HBsAg decline
timeFrame: 40 weeks
measure: Measurement of HBV-DNA decline
timeFrame: 40 weeks
measure: Measurement of HBV-pgRNA decline
timeFrame: 40 weeks
measure: Measurement of HBcrAg decline
timeFrame: 40 weeks
measure: Concentration of EYP001a - Pharmacokinetic
timeFrame: 20 weeks
measure: Concentration of C4 - Pharmacodynamic biomarker
timeFrame: 40 weeks
measure: Concentration of FGF19 - Pharmacodynamic biomarker
timeFrame: 40 weeks
measure: Concentration of Bile Acids - Pharmacodynamic biomarker
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: ENYO PHARMA Investigative site HK01
city: Busan
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR01
city: Kaohsiung
country: Taiwan
facility: ENYO PHARMA Investigative site TW03
city: Kaohsiung
country: Taiwan
facility: ENYO PHARMA Investigative site TW04
city: Taipei
country: Taiwan
facility: ENYO PHARMA Investigative site TW01
city: Taoyuan
country: Taiwan
facility: ENYO PHARMA Investigative site TW02
Study officials:
References: