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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03272009




Registration number
NCT03272009
Ethics application status
Date submitted
31/08/2017
Date registered
5/09/2017
Date last updated
21/08/2018

Titles & IDs
Public title
Evaluation of the Safety and Pharmacology of EYP001 in HBV Subjects
Scientific title
A Randomized, Double-blind, Placebo-controlled Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the FXR-agonist EYP001a in Chronically HBV Infected Subjects
Secondary ID [1] 0 0
2017-002211-33
Secondary ID [2] 0 0
EYP001-103
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 - peg-interferon alfa-2a

Experimental: Treatment A - oral EYP001a

Experimental: Treatment B - oral EYP001a

Experimental: Treatment C - oral EYP001a

Experimental: Treatment D - oral EYP001a

Placebo Comparator: Treatment E - oral placebo

Active Comparator: Treatment F - oral Entecavir

Experimental: Treatment G - oral EYP001a plus subcutaneous injection of Peg-INFa2a

Experimental: Treatment H - oral EYP001a plus subcutaneous injection of Peg-INFa2a

Placebo Comparator: Treatment I - oral placebo plus subcutaneous injection of Peg-INFa2a


Treatment: Drugs: EYP001a
Capsules administered orally. Number of morning and evening capsules depending on treatment arm

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

Treatment: Drugs: Entecavir
Tablets administered orally

Treatment: Drugs: peg-interferon alfa-2a
Ready-to-Use pre-filled syringes for subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Type and frequencies of adverse events
Timepoint [1] 0 0
Day 1 through Day 35
Secondary outcome [1] 0 0
Maximum plasma concentration (Cmax) of EYP001
Timepoint [1] 0 0
Day 1 through Day 35
Secondary outcome [2] 0 0
Time to reach maximum concentration (Tmax) after EYP001 administration
Timepoint [2] 0 0
Day 1 through Day 35
Secondary outcome [3] 0 0
Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001
Timepoint [3] 0 0
Day 1 through Day 35
Secondary outcome [4] 0 0
Bile acid precursor C4 (7ahydroxy-4-cholesten-3-one)
Timepoint [4] 0 0
Day 1 through Day 35
Secondary outcome [5] 0 0
Fibroblast growth factor 19 (FGF19)
Timepoint [5] 0 0
Day 1 through Day 35

Eligibility
Key inclusion criteria
1. Have given voluntary written informed consent;

2. 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

3. Is anti-HBV treatment naive or treatment experienced (see also exclusion criterion
#3).

4. Gender: male or female.

5. Age: 18 to 65 years inclusive.

6. Body mass index (BMI): 17.0-35.0 kg/m2 inclusive.

7. Has clinical chemistry, hematology, coagulation and urinalysis tests within normal,
allowable limits (with the exception of alanine aminotransferase [ALT]); see inclusion
criterion #10); if there is an out of range value, the result must be considered
clinically non-significant by the investigator in order to be eligible.

8. 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

9. 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.

10. ALT at screening = 5 x upper limit of normal (ULN).

11. 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.

12. 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.

13. Female subjects of child-bearing potential, with a fertile male sexual partner, should
be willing to use adequate contraception from screening until 90 days after the
follow-up visit. Adequate contraception is defined as using hormonal contraceptives or
an intrauterine device combined with at least 1 of the following forms of
contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in
accordance with the lifestyle of the subject, is acceptable.

14. Male subjects, if not surgically sterilized, should be willing to use adequate
contraception and not donate sperm from the Day 1 visit to the clinical research
centre until 90 days after the follow-up visit. Adequate contraception for the male
subject (and his female partner) is defined as using hormonal contraceptives or an
intrauterine device combined with at least 1 of the following forms of contraception:
a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with
the lifestyle of the subject is acceptable.

15. At screening, has no recent (<3 months) history of any clinically significant
conditions, which, in the opinion of the investigator, would jeopardize the safety of
the subject or impact the validity of the study results.

16. Willingness to abstain from alcohol from 48 hours prior to each study visit to the
clinical research centre.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Employee of a CRO participating in this study or the Sponsor.

2. Has certain or probable compensated liver cirrhosis documented by at least 2 of the
following:

1. Optional assessment: has documented liver histology Metavir score (F4), Ishak >5
or Scheuer (F4)

2. Mandatory assessment: has presence or history of ascites, spontaneous bacterial
peritonitis, esophageal varices, hepatic encephalopathy

3. Mandatory assessment: platelet count below 90,000/uL within 12 months of
screening visit

4. 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

5. Optional assessment: has positive elastography within 6 months of screening visit
(Fibroscan or Shearwave Aixplorer)

6. Optional assessment: has abnormal liver imaging (CT/US/MRI) consistent with a
lobular/nodular liver and cirrhosis or indirect signs of portal hypertension.

3. 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.

4. Co-infection with active hepatitis C virus (HCV, except for patients with sustained
viral response SVR, who can be included).

5. 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.

6. 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.

7. Has clinically relevant immunosuppression from, but not limited to immunodeficiency
conditions such as common variable hypogammaglobulinemia.

8. 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]).

9. 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.

10. Has any known pre-existing medical or psychiatric condition that could interfere with
the subject's ability to provide informed consent or participate in study conduct, or
that may confound study findings.

11. Has a history of long QT syndrome.

12. Has a history of clinically significant gastrointestinal disease, especially peptic
ulcerations, gastrointestinal bleeding, ulcerative colitis, Crohn's disease or
Inflammatory Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine,
oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition
which, in the opinion of the investigator, would jeopardize the safety of the subject
or impact the validity of the study results.

13. Has participated in any drug study within 40 days prior to the first drug
administration in the current study. Note: Part A participation to this study is
acceptable and not an exclusion criteria when considering eligibility for Part B,
under the condition that follow-up visit of Part A has been completed and no
investigational product related SAEs have occurred during Part A.

14. Has an uncontrolled ongoing illness at screening (e.g., active viral infection).

15. Has had major surgery within 30 days prior to the first drug administration, or within
6 months for gastrointestinal surgery prior to the first drug administration.

16. Has a history of relevant drug and/or food allergies.

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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/07/2018
Sample size
Target
Accrual to date
Final
73
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Scientia Clinical Research Limited - Sydney
Recruitment hospital [2] 0 0
Linear Clinical Research Limited - Perth
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Amsterdam
Country [2] 0 0
Netherlands
State/province [2] 0 0
Rotterdam
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
Thailand
State/province [6] 0 0
Bangkok

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
CPR Pharma Services Pty Ltd, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03272009
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Henk W Reesink, MD
Address 0 0
Academic Medical Centre AMC Amsterdam
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