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

Primary Purpose

Hepatitis B, Chronic

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

EYP001a

Placebo

Nucleotide analogue (Entecavir or Tenofovir Disoproxil)

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental Arm

Control Arm

Arm Description

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

Control Arm: Placebo + NA daily (12 patients)

Outcomes

Primary Outcome Measures

HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment

Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment

Secondary Outcome Measures

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

Full Information

NCT ID

NCT04465916

First Posted

July 6, 2020

Last Updated

October 11, 2022

Sponsor

Enyo Pharma

Collaborators

Novotech (Australia) Pty Limited, Synteract, Inc., Eurofins, Parexel

1. Study Identification

Unique Protocol Identification Number

NCT04465916

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Terminated

Why Stopped

DSMC reviewed results of 26 subjects. New randomizations were stopped. Already randomized subjects were followed up to W40.

Study Start Date

May 12, 2020 (Actual)

Primary Completion Date

June 17, 2021 (Actual)

Study Completion Date

November 25, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Enyo Pharma

Collaborators

Novotech (Australia) Pty Limited, Synteract, Inc., Eurofins, Parexel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Masking Description

Triple blind

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Arm

Arm Type

Experimental

Arm Description

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

Arm Title

Control Arm

Arm Type

Placebo Comparator

Arm Description

Control Arm: Placebo + NA daily (12 patients)

Intervention Type

Drug

Intervention Name(s)

EYP001a

Intervention Description

Oral tablets

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Oral tablets

Intervention Type

Drug

Intervention Name(s)

Nucleotide analogue (Entecavir or Tenofovir Disoproxil)

Intervention Description

Oral tablets

Primary Outcome Measure Information:

Title

HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment

Description

Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment

Time Frame

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 Outcome Measure Information:

Title

Virologic Failure Rate

Description

Time Frame

40 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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: Estimated glomerular filtration rate <60 mL/min/1.73 m2 (the Modification of Diet in Renal Disease formula). Thyroid-stimulating hormone >1.5× ULN or abnormal free triiodothyronine or free thyroxine.

Overall Study Officials: