Evaluation of the Safety and Pharmacology of EYP001 in HBV Subjects

NCT03272009 | Completed Phase 1 DMC

• 2 other identifiers: EYP001-1032017-002211-33
• Study Type: interventional
• Target: 73
• Locations: 4 countries
• Sites: 9

Brief Summary

Bile acids regulating farnesoid X receptor (FXR) interact with hepatitis B virus replication. EYP001a is a selective, synthetic FXR agonist under development for the treatment of hepatitis B. This Phase 1b study is designed primarily to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of EYP001a in chronically HBV infected subjects.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Type and frequencies of adverse events

  Day 1 through Day 35

Secondary Outcomes (5)

• Maximum plasma concentration (Cmax) of EYP001

  Day 1 through Day 35

• Time to reach maximum concentration (Tmax) after EYP001 administration

  Day 1 through Day 35

• Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001

  Day 1 through Day 35

• Bile acid precursor C4 (7αhydroxy-4-cholesten-3-one)

  Day 1 through Day 35

• Fibroblast growth factor 19 (FGF19)

  Day 1 through Day 35

Study Arms (9)

Treatment A

EXPERIMENTAL

oral EYP001a

Drug: EYP001a

Treatment B

EXPERIMENTAL

oral EYP001a

Drug: EYP001a

Treatment C

EXPERIMENTAL

oral EYP001a

Drug: EYP001a

Treatment D

EXPERIMENTAL

oral EYP001a

Drug: EYP001a

Treatment E

PLACEBO COMPARATOR

oral placebo

Drug: Placebo

Treatment F

ACTIVE COMPARATOR

oral Entecavir

Drug: Entecavir

Treatment G

EXPERIMENTAL

oral EYP001a plus subcutaneous injection of Peg-INFα2a

Drug: EYP001a; Drug: peg-interferon alfa-2a

Treatment H

EXPERIMENTAL

oral EYP001a plus subcutaneous injection of Peg-INFα2a

Drug: EYP001a; Drug: peg-interferon alfa-2a

Treatment I

PLACEBO COMPARATOR

oral placebo plus subcutaneous injection of Peg-INFα2a

Drug: Placebo; Drug: peg-interferon alfa-2a

Interventions

EYP001a DRUG

Capsules administered orally. Number of morning and evening capsules depending on treatment arm

Treatment A; Treatment B; Treatment C; Treatment D; Treatment G; Treatment H

Placebo DRUG

Placebo capsules for oral administration, identical in appearance to the EYP001a capsules

Treatment E; Treatment I

Entecavir DRUG

Tablets administered orally

Treatment F

peg-interferon alfa-2a DRUG

Ready-to-Use pre-filled syringes for subcutaneous injection

Treatment G; Treatment H; Treatment I

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given voluntary written informed consent;
• Have a documented medical history of chronic HBV infection (within 12 months of screening visit), both results:
• Documented positive hepatitis B surface antigen (HBsAg) and
• Documented HBV DNA \> 1000 IU/mL
• Gender: male or female.
• Age: 18 to 65 years inclusive.
• Body mass index (BMI): 17.0-35.0 kg/m2 inclusive.
• Vital signs after at least 5 minutes resting in supine position at screening within the following ranges:
• systolic blood pressure: between 90 mm Hg and 145 mm Hg
• diastolic blood pressure: between 45 mm Hg and 90 mm Hg
• heart rate: between 40 bpm and 100 bpm
• Have no clinically significant abnormal 12-lead automatic electrocardiogram (ECG) (incomplete right bundle branch block can be accepted) at screening: PR interval between 120 ms -and 210 ms, QRS-duration \< 120 ms, QTc-interval (Fridericia's) ≤ 450 msec.
• ALT at screening ≤ 5 x upper limit of normal (ULN).
• Agrees to abstain from all medication, including non-prescription and prescription medication for 28 days prior to the Day 1 study visit, except for authorized medications (such as hormonal contraceptives for females, vitamins prescribed per label dosages and paracetamol). On a case-by-case basis, regular co-medication either as defined on the medication exception list or as documented by written approval from the sponsor as acceptable prior to randomization, will not be considered as a deviation from this criterion.
• At screening, females must be non-pregnant and non-lactating, or of non-childbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year post-menopausal \[amenorrhea duration of 12 consecutive months); non-pregnancy will be confirmed for all females by a pregnancy test conducted at screening and at follow-up visit.

You may not qualify if:

• Employee of a CRO participating in this study or the Sponsor.
• Has certain or probable compensated liver cirrhosis documented by at least 2 of the following:
• Optional assessment: has documented liver histology Metavir score (F4), Ishak \>5 or Scheuer (F4)
• Mandatory assessment: has presence or history of ascites, spontaneous bacterial peritonitis, esophageal varices, hepatic encephalopathy
• Mandatory assessment: platelet count below 90,000/uL within 12 months of screening visit
• Optional assessment: positive indirect blood test of APRI or FIB4 or positive direct blood test Fibrosure, Fibrotest, or FibroSpect within 12 months of screening visit
• Optional assessment: has positive elastography within 6 months of screening visit (Fibroscan or Shearwave Aixplorer)
• Optional assessment: has abnormal liver imaging (CT/US/MRI) consistent with a lobular/nodular liver and cirrhosis or indirect signs of portal hypertension.
• Subject is HBV treatment experienced AND currently on anti-HBV treatment during the 30 days (or 5 half-lives of the considered anti-HBV drug, whichever is longer) before the first investigational product administration and until the last study visit.
• Co-infection with active hepatitis C virus (HCV, except for patients with sustained viral response SVR, who can be included).
• Co-infection with human immunodeficiency virus (HIV) Note: hepatitis D virus (HDV) status is not required for randomization and if not available can be established during the Day 1 visit with baseline PD virology assessments.
• Receives or plans to receive systemic immunosuppressive or immunomodulating medications (e.g. IFN) during the study or ≤ 4 months prior to the first investigational product administration.
• Has clinically relevant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Clinical diagnosis of substance abuse during ≤ 12 months prior to screening with narcotics or cocaine or with alcohol (regular consumption \> 21 units/week \[men\] and \> 14 units/week \[women\]; 1 unit = 1⁄2 pint of beer, 25 mL shot of 40% spirit or a 125 mL glass of wine. Expressed in g/day: \> 30 g/day \[men\] and \> 20 g/day \[women\]).
• Has a positive drug urine screen (cocaine, phencyclidine, amphetamines (incl. methamphetamines), opiates (incl. heroin, codeine and morphine), benzodiazepines, barbiturates, methadone or alcohol screen. Subjects who admit the occasional use of cannabis will not be excluded as long as they are able to abstain from cannabis when they are assessed at study visits.

Sponsors & Collaborators

• Enyo Pharma: lead
• CPR Pharma Services Pty Ltd, Australia: collaborator

Study Sites (9)

Scientia Clinical Research Limited

Sydney, New South Wales, 2031, Australia

Location

Linear Clinical Research Limited

Perth, Western Australia, 6009, Australia

Location

Academic Medical Centre (AMC)

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Klinika Chorób Zakaźnych I Hepatologii UMB

Bialystok, Poland

Location

Klinika Chorób Zakaźnych

Kielce, 25-317, Poland

Location

HepID

Lublin, Poland

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Hospital for Tropical Diseases

Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henk W Reesink, MD

  Academic Medical Centre AMC Amsterdam

  PRINCIPAL INVESTIGATOR

• Stephan Riordan

  Scientia Clinical Research Limited Sydney

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 5, 2017
• Study Start: September 21, 2017
• Primary Completion: July 30, 2018
• Study Completion: July 30, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

AU (2); PL (3); NL (2); TH (2)