Clinical trial NCT04465916: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Enyo Pharma
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
name: Synteract, Inc.
name: Eurofins
name: Parexel
First posted: 2020-07-10
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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:

  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.

Primary outcomes:
measure: HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment
timeFrame: 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 outcomes:
measure: Virologic Failure Rate
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: ENYO PHARMA Investigative site AU02
city: Melbourne
country: Australia
facility: ENYO PHARMA Investigative site AU01
city: Melbourne
country: Australia
facility: ENYO PHARMA Investigative site AU03
city: Melbourne
country: Australia
facility: ENYO PHARMA Investigative site AU04
city: Hong Kong
country: Hong Kong
facility: ENYO PHARMA Investigative site HK01
city: Pusan
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR04
city: Pusan
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR07
city: Seongnam
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR05
city: Seoul
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR01
city: Seoul
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR02
city: Seoul
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR03
city: Séoul
country: Korea, Republic of
facility: ENYO PHARMA Investigative site KR06
city: Białystok
country: Poland
facility: ENYO PHARMA Investigative site PL01
city: Kielce
country: Poland
facility: ENYO PHARMA Investigative site PL06
city: Lublin
country: Poland
facility: ENYO PHARMA Investigative site PL02
city: Warszawa
country: Poland
facility: ENYO PHARMA Investigative site PL03
city: Zawiercie
country: Poland
facility: ENYO PHARMA Investigative site PL04
city: Łódź
country: Poland
facility: ENYO PHARMA Investigative site PL05
Study officials:
affiliation: Pusan, South Korea
name: ENYO PHARMA Investigative site KR04
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul, South Korea
name: ENYO PHARMA Investigative site KR03
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul, South Korea
name: ENYO PHARMA Investigative site KR02
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul, South Korea
name: ENYO PHARMA Investigative site KR01
role: PRINCIPAL_INVESTIGATOR
affiliation: Kielce, Poland
name: ENYO PHARMA Investigative site PL06
role: PRINCIPAL_INVESTIGATOR
affiliation: Łódź, Poland
name: ENYO PHARMA Investigative site PL05
role: PRINCIPAL_INVESTIGATOR
affiliation: Zawiercie, Poland
name: ENYO PHARMA Investigative site PL04
role: PRINCIPAL_INVESTIGATOR
affiliation: Warszawa, Poland
name: ENYO PHARMA Investigative site PL03
role: PRINCIPAL_INVESTIGATOR
affiliation: Lublin, Poland
name: ENYO PHARMA Investigative site PL02
role: PRINCIPAL_INVESTIGATOR
affiliation: Białystok, Poland
name: ENYO PHARMA Investigative site PL01
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne, Australia
name: ENYO PHARMA Investigative site AU04
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne, Australia
name: ENYO PHARMA Investigative site AU03
role: PRINCIPAL_INVESTIGATOR
affiliation: Brisbane, Australia
name: ENYO PHARMA Investigative site AU02
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne, Australia
name: ENYO PHARMA Investigative site AU01
role: PRINCIPAL_INVESTIGATOR
affiliation: Hong Kong, Hong Kong
name: ENYO PHARMA Investigative site HK01
role: PRINCIPAL_INVESTIGATOR
affiliation: Seongnam, South Korea
name: ENYO PHARMA Investigative site KR05
role: PRINCIPAL_INVESTIGATOR
affiliation: Séoul, South Korea
name: ENYO PHARMA Investigative site KR06
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan, South Korea
name: ENYO PHARMA Investigative site KR07
role: PRINCIPAL_INVESTIGATOR
References: