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

• Sponsor: Enyo Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04365933
• Collaborator: (none)
• Enrollment: 20
• Locations: 6
• Arms: 2
• Actual Duration (Months): 18.2
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: EYP001a; Drug: Entecavir; Drug: Pegylated interferon alpha2a	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 25, 2020
• Actual Primary Completion Date: Jun 16, 2021
• Actual Study Completion Date: Nov 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW	Drug: EYP001a; Oral tablets; Drug: Entecavir; Oral tablets; Drug: Pegylated interferon alpha2a; Subcutaneous
Experimental: Arm 2 EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW	Drug: EYP001a; Oral tablets; Drug: Pegylated interferon alpha2a; Subcutaneous

Outcome Measures

Primary Outcome Measures

1. Number of Treatment-emergent adverse events [16 weeks]

   Number of Treatment-emergent adverse events including serious adverse events

2. Measurement of HBsAg decline [16 weeks]

   Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period

Secondary Outcome Measures

1. Measurement of HBsAg decline [40 weeks]

   Measurement of HBsAg decline (Δ log10)

2. Measurement of HBV-DNA decline [40 weeks]

   Measurement of HBV-DNA decline (Δ log10)

3. Measurement of HBV-pgRNA decline [40 weeks]

   Measurement of HBV-pgRNA decline (Δ log10)

4. Measurement of HBcrAg decline [40 weeks]

   Measurement of HBcrAg decline (Δ log10)

5. Concentration of EYP001a - Pharmacokinetic [20 weeks]

   Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry

6. Concentration of C4 - Pharmacodynamic biomarker [40 weeks]

   Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)

7. Concentration of FGF19 - Pharmacodynamic biomarker [40 weeks]

   Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)

8. Concentration of Bile Acids - Pharmacodynamic biomarker [40 weeks]

   Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ENYO PHARMA Investigative site HK01	Hong Kong		Hong Kong
2	ENYO PHARMA Investigative site KR01	Busan		Korea, Republic of
3	ENYO PHARMA Investigative site TW03	Kaohsiung		Taiwan
4	ENYO PHARMA Investigative site TW04	Kaohsiung		Taiwan
5	ENYO PHARMA Investigative site TW01	Taipei		Taiwan
6	ENYO PHARMA Investigative site TW02	Taoyuan		Taiwan

Sponsors and Collaborators

• Enyo Pharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Enyo Pharma
• ClinicalTrials.gov Identifier: NCT04365933
• Other Study ID Numbers: EYP001-203
• First Posted: Apr 28, 2020
• Last Update Posted: Aug 25, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Interferons; Interferon-alpha; Interferon alpha-2; Entecavir; Peginterferon alfa-2a

Study Results

No Results Posted as of Aug 25, 2022