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

Enyo Pharma

Status and phase: Terminated; Phase 2

Conditions: Hepatitis B, Chronic

Treatments: Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil); Drug: Placebo; Drug: EYP001a

Study type: Interventional

Funder types: Industry

Identifiers

NCT04465916

EYP001-201

Details and patient eligibility

About

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.

Full 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).

Enrollment: 26 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

26 participants in 2 patient groups, including a placebo group

Experimental Arm

Experimental group

Description:

Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)

Treatment:

Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil)

Drug: EYP001a

Control Arm

Placebo Comparator group

Description:

Control Arm: Placebo + NA daily (12 patients)

Treatment:

Drug: Nucleotide analogue (Entecavir or Tenofovir Disoproxil)

Drug: Placebo