We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04465916




Registration number
NCT04465916
Ethics application status
Date submitted
6/07/2020
Date registered
10/07/2020
Date last updated
1/04/2021

Titles & IDs
Public title
Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD)
Scientific 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
Secondary ID [1] 0 0
EYP001-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EYP001a
Treatment: Drugs - Placebo
Treatment: Drugs - Entecavir
Treatment: Drugs - Tenofovir Disoproxil

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

Placebo Comparator: Control Arm - Control Arm: Placebo + NA daily (12 patients)


Treatment: Drugs: EYP001a
Oral tablets

Treatment: Drugs: Placebo
Oral tablets

Treatment: Drugs: Entecavir
Oral tablets

Treatment: Drugs: Tenofovir Disoproxil
Oral tablets

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
HBsAg change - Efficacy assessed as HBsAg change (? log10) from Day 1 to Week 16 of treatment
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
HBsAg responder rate change - HBsAg responder rate (change from baseline = 1.0 on the log10 scale) at Week 16 of treatment and Weeks 20, 28 and 40 of follow-up.
Timepoint [1] 0 0
40 weeks
Secondary outcome [2] 0 0
HBsAg responder rate change - HBsAg responder rate (change from baseline = 0.5 on the log10 scale) at Weeks 12 and 16 of treatment and Weeks 20, 28 and 40 of follow up.
Timepoint [2] 0 0
40 weeks
Secondary outcome [3] 0 0
HBsAg loss rate - HBsAg loss rate (percent of patients with HBsAg < lower limit of quantification [LLOQ]) at Week 16 of treatment and Weeks 20, 28 and 40 of follow-up
Timepoint [3] 0 0
40 weeks
Secondary outcome [4] 0 0
HBsAg loss rate - HBsAg loss rate (Proportion of results that are Target Not Detected versus Target Detected) at Week 16 of treatment and Weeks 20, 28 and 40 of follow-up
Timepoint [4] 0 0
40 weeks
Secondary outcome [5] 0 0
Relapse rate HBsAg - Relapse rate HBsAg (percent of patients who became negative [HBsAg < LLOQ], then increased with HBsAg > LLOQ) at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up period
Timepoint [5] 0 0
40 weeks
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
40 weeks
Secondary outcome [7] 0 0
HBV-pgRNA change - HBV-pgRNA change (? log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of maintenance period
Timepoint [7] 0 0
40 weeks
Secondary outcome [8] 0 0
HBcrAg change - HBcrAg change (? log10) from Day 1 to Weeks 4, 8, 12, 16 of treatment period and Week 40 of maintenance period
Timepoint [8] 0 0
40 weeks
Secondary outcome [9] 0 0
HBeAg quantification - HBeAg quantification for HBeAg pos patients and changes at Week 16 of treatment and Week 40 of follow-up
Timepoint [9] 0 0
40 weeks
Secondary outcome [10] 0 0
Fibroscan VCTE change - Fibroscan VCTE change from screening value to Weeks 16 and 40 or ET value
Timepoint [10] 0 0
40 weeks
Secondary outcome [11] 0 0
Safety (Adverse Events) - Safety and Tolerability assessed as: AEs including serious adverse events [SAEs]
Timepoint [11] 0 0
40 weeks
Secondary outcome [12] 0 0
PK (EYP001a/placebo blood dosage) - PK assessed as:
o Plasma concentration of EYP001a or any relevant active metabolites (as identified in an ongoing phase 1 study).
Timepoint [12] 0 0
16 weeks
Secondary outcome [13] 0 0
PD : C4 - PD markers: Plasma C4 (7a-hydroxy-4-cholesten-3-one)
Timepoint [13] 0 0
40 weeks
Secondary outcome [14] 0 0
PD: FGF19 - FGF19: Fibroblast Growth Factor 19
Timepoint [14] 0 0
40 weeks
Secondary outcome [15] 0 0
PD: BA - Biles Acids (Plasma primary and secondary BAs)
Timepoint [15] 0 0
40 weeks

Eligibility
Key inclusion criteria
Main

- 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
ENYO PHARMA Investigative site AU02 - Brisbane
Recruitment hospital [2] 0 0
ENYO PHARMA Investigative site AU01 - Melbourne
Recruitment hospital [3] 0 0
ENYO PHARMA Investigative site AU03 - Melbourne
Recruitment hospital [4] 0 0
ENYO PHARMA Investigative site AU04 - Melbourne
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Korea, Republic of
State/province [1] 0 0
Busan
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul
Country [3] 0 0
Poland
State/province [3] 0 0
Bialystok
Country [4] 0 0
Poland
State/province [4] 0 0
Kielce
Country [5] 0 0
Poland
State/province [5] 0 0
Lublin
Country [6] 0 0
Poland
State/province [6] 0 0
Warszawa
Country [7] 0 0
Poland
State/province [7] 0 0
Zawiercie
Country [8] 0 0
Poland
State/province [8] 0 0
Lódz

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Enyo Pharma
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Synteract, Inc.
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Eurofins
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Parexel
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04465916
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ENYO PHARMA Investigative site KR04
Address 0 0
Busan, South Korea
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications