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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04465916
• Other study ID #: EYP001-201
• Status: Terminated
• Phase: Phase 2
• Start date: May 12, 2020
• Est. completion date: November 25, 2021

Study information

• Verified date: October 2022
• Source: Enyo Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: November 25, 2021
• Est. primary completion date: June 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• EYP001a
Oral tablets
• Placebo
Oral tablets
• Nucleotide analogue (Entecavir or Tenofovir Disoproxil)
Oral tablets

Locations

Country	Name	City	State
Australia	ENYO PHARMA Investigative site AU02	Brisbane
Australia	ENYO PHARMA Investigative site AU01	Melbourne
Australia	ENYO PHARMA Investigative site AU03	Melbourne
Australia	ENYO PHARMA Investigative site AU04	Melbourne
Hong Kong	ENYO PHARMA Investigative site HK01	Hong Kong
Korea, Republic of	ENYO PHARMA Investigative site KR04	Pusan
Korea, Republic of	ENYO PHARMA Investigative site KR07	Pusan
Korea, Republic of	ENYO PHARMA Investigative site KR05	Seongnam
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	Seoul
Korea, Republic of	ENYO PHARMA Investigative site KR06	Séoul
Poland	ENYO PHARMA Investigative site PL01	Bialystok
Poland	ENYO PHARMA Investigative site PL06	Kielce
Poland	ENYO PHARMA Investigative site PL05	Lódz
Poland	ENYO PHARMA Investigative site PL02	Lublin
Poland	ENYO PHARMA Investigative site PL03	Warszawa
Poland	ENYO PHARMA Investigative site PL04	Zawiercie

Sponsors (5)

Lead Sponsor	Collaborator
Enyo Pharma	Eurofins, Novotech (Australia) Pty Limited, Parexel, Synteract, Inc.

Countries where clinical trial is conducted

Australia,  Hong Kong,  Korea, Republic of,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBsAg Change (? log10) From Day 1 to Week 16 of Treatment	Efficacy of Vonafexor on top of NA assessed as HBsAg decline (? 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	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