Hepatitis B, ChronicPhase 1NCT03272009
Evaluation of the Safety and Pharmacology of EYP001 in HBV Subjects
A Phase 1 study testing EYP001a, Entecavir and peg-interferon alfa-2a in people with Hepatitis B, Chronic, run by Enyo Pharma at 9 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- EYP001a, Entecavir and peg-interferon alfa-2a
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 73 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 21 Sep 2017to 30 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Is anti-HBV treatment naive or treatment experienced (see also exclusion criterion #3).
- Gender: male or female.
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- Age: 18 to 65 years inclusive.
- Body mass index (BMI): 17.0-35.0 kg/m2 inclusive.
- 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.
- 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.
- 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.
- 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.
- 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.
- Willingness to abstain from alcohol from 48 hours prior to each study visit to the clinical research centre.
Who cannot join
- 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
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- 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.
- 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.
- Has a history of long QT syndrome.
- 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.
- 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.
- Has an uncontrolled ongoing illness at screening (e.g., active viral infection).
- 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.
- Has a history of relevant drug and/or food allergies.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Poland3 sites
Klinika Chorób Zakaźnych I Hepatologii UMB
Bialystok
Klinika Chorób Zakaźnych
Kielce, 25-317
HepID
Lublin
Australia2 sites
Linear Clinical Research Limited
Perth, Western Australia, 6009
Scientia Clinical Research Limited
Sydney, New South Wales, 2031
Netherlands2 sites
Academic Medical Centre (AMC)
Amsterdam
Erasmus MC
Rotterdam
Thailand2 sites
King Chulalongkorn Memorial Hospital
Bangkok, 10330
Hospital for Tropical Diseases
Bangkok, 10400
About this study
Official 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
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.
Read the detailed description
This is a multicenter, randomized, double-blind, placebo-controlled two-part trial.
In Part A, EYP001a will be administered as 29 days monotherapy. Three dose-levels and 2 dosing regimens of EYP001a will be explored against placebo. The design also includes an open-label standard of care Entecavir monotherapy arm (comparator). Subjects will be randomly assigned to one of the 6 treatment arms:
- Treatment A: oral EYP001a
- Treatment B: oral EYP001a
- Treatment C: oral EYP001a
- Treatment D: oral EYP001a
- Treatment E: oral placebo
- Treatment F: oral Entecavir
In Part B, EYP001a or placebo will be administered as 29 days combination therapy with the standard of care Peg-IFNα2a. Subjects will be randomly assigned to one of the 3 treatment arms:
- Treatment G: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous injection
- Treatment H: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous injection
- Treatment I: oral placebo plus open label Peg-INFα2a administered as subcutaneous injection
Subjects enrolled in Part A are eligible for participation in Part B.
Participation will include a 40 day screening period, a 29 day treatment period and a 6 day follow-up evaluation period. For subjects who participate in both Parts A and B, a 14 washout period between Parts A and B will be included.
The safety and tolerability of EYP001a will be assessed by evaluating physical examinations, vital signs, ECGs, clinical laboratory parameters, and adverse events.
- Conditions
- Hepatitis B, Chronic
- Being tested
- EYP001a, Placebo, Entecavir, peg-interferon alfa-2a
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EYP001aDrug
Capsules administered orally. Number of morning and evening capsules depending on treatment arm
PlaceboDrug
Placebo capsules for oral administration, identical in appearance to the EYP001a capsules
EntecavirDrug
Tablets administered orally
peg-interferon alfa-2aDrug
Ready-to-Use pre-filled syringes for subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | oral EYP001a Receives: Drug: EYP001a |
| Treatment B | Experimental | oral EYP001a Receives: Drug: EYP001a |
| Treatment C | Experimental | oral EYP001a Receives: Drug: EYP001a |
| Treatment D | Experimental | oral EYP001a Receives: Drug: EYP001a |
| Treatment E | Placebo comparator | oral placebo Receives: Drug: Placebo |
| Treatment F | Active comparator | oral Entecavir Receives: Drug: Entecavir |
| Treatment G | Experimental | oral EYP001a plus subcutaneous injection of Peg-INFα2a Receives: Drug: EYP001a; Drug: peg-interferon alfa-2a |
| Treatment H | Experimental | oral EYP001a plus subcutaneous injection of Peg-INFα2a Receives: Drug: EYP001a; Drug: peg-interferon alfa-2a |
| Treatment I | Placebo comparator | oral placebo plus subcutaneous injection of Peg-INFα2a Receives: Drug: Placebo; Drug: peg-interferon alfa-2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Type and frequencies of adverse events
Measured: Day 1 through Day 35
Secondary outcomes (5)
Maximum plasma concentration (Cmax) of EYP001
Measured: Day 1 through Day 35
Time to reach maximum concentration (Tmax) after EYP001 administration
Measured: Day 1 through Day 35
Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001
Measured: Day 1 through Day 35
Bile acid precursor C4 (7αhydroxy-4-cholesten-3-one)
Measured: Day 1 through Day 35
Fibroblast growth factor 19 (FGF19)
Measured: Day 1 through Day 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2017
- Study start21 Sep 2017
- Primary completion30 Jul 2018
- Study completion30 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enyo Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Responsible party
- Sponsor
- Investigators
- Henk W Reesink, MD, Principal investigator, Academic Medical Centre AMC AmsterdamStephan Riordan, Principal investigator, Scientia Clinical Research Limited Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03272009
- Sponsor's protocol ID
- EYP001-103
- Other IDs
- 2017-002211-33, 2017
- Status last verified
- Aug 2018
- First submitted
- 31 Aug 2017
- Last updated
- 21 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03272009
- Acronym / sponsor ID
- EYP001-103
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Enyo PharmaIndustry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Study start
- 21 Sep 2017 (actual)
- Primary completion
- 30 Jul 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 5 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled two-part trial.
In Part A, EYP001a will be administered as 29 days monotherapy. Three dose-levels and 2 dosing regimens of EYP001a will be explored against placebo. The design also includes an open-label standard of care Entecavir monotherapy arm (comparator). Subjects will be randomly assigned to one of the 6 treatment arms:
- Treatment A: oral EYP001a
- Treatment B: oral EYP001a
- Treatment C: oral EYP001a
- Treatment D: oral EYP001a
- Treatment E: oral placebo
- Treatment F: oral Entecavir
In Part B, EYP001a or placebo will be administered as 29 days combination therapy with the standard of care Peg-IFNα2a. Subjects will be randomly assigned to one of the 3 treatment arms:
- Treatment G: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous injection
- Treatment H: oral EYP001a plus open label Peg-INFα2a administered as subcutaneous injection
- Treatment I: oral placebo plus open label Peg-INFα2a administered as subcutaneous injection
Subjects enrolled in Part A are eligible for participation in Part B.
Participation will include a 40 day screening period, a 29 day treatment period and a 6 day follow-up evaluation period. For subjects who participate in both Parts A and B, a 14 washout period between Parts A and B will be included.
The safety and tolerability of EYP001a will be assessed by evaluating physical examinations, vital signs, ECGs, clinical laboratory parameters, and adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: EYP001aoral EYP001a |
| Treatment B | Experimental | Drug: EYP001aoral EYP001a |
| Treatment C | Experimental | Drug: EYP001aoral EYP001a |
| Treatment D | Experimental | Drug: EYP001aoral EYP001a |
| Treatment E | Placebo comparator | Drug: Placebooral placebo |
| Treatment F | Active comparator | Drug: Entecaviroral Entecavir |
| Treatment G | Experimental | Drug: EYP001a, Drug: peg-interferon alfa-2aoral EYP001a plus subcutaneous injection of Peg-INFα2a |
| Treatment H | Experimental | Drug: EYP001a, Drug: peg-interferon alfa-2aoral EYP001a plus subcutaneous injection of Peg-INFα2a |
| Treatment I | Placebo comparator | Drug: Placebo, Drug: peg-interferon alfa-2aoral placebo plus subcutaneous injection of Peg-INFα2a |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Have given voluntary written informed consent;
- Have a documented medical history of chronic HBV infection (within 12 months of screening visit), both results:
- Is anti-HBV treatment naive or treatment experienced (see also exclusion criterion #3).
- Gender: male or female.
- Age: 18 to 65 years inclusive.
Key exclusion criteria (22 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EYP001aCapsules administered orally. Number of morning and evening capsules depending on treatment arm | Drug | Treatment A, Treatment B, Treatment C, Treatment D, Treatment G, Treatment H |
| PlaceboPlacebo capsules for oral administration, identical in appearance to the EYP001a capsules | Drug | Treatment E, Treatment I |
| EntecavirTablets administered orally | Drug | Treatment F |
| peg-interferon alfa-2aReady-to-Use pre-filled syringes for subcutaneous injection | Drug | Treatment G, Treatment H, Treatment I |
Primary outcome
Type and frequencies of adverse events
Time frame: Day 1 through Day 35
5 secondary outcomes
Maximum plasma concentration (Cmax) of EYP001
Time frame: Day 1 through Day 35
Time to reach maximum concentration (Tmax) after EYP001 administration
Time frame: Day 1 through Day 35
Area under the concentration-time curve from time 0 to last measurable concentration (AUC0-6h) of EYP001
Time frame: Day 1 through Day 35
Bile acid precursor C4 (7αhydroxy-4-cholesten-3-one)
Time frame: Day 1 through Day 35
Fibroblast growth factor 19 (FGF19)
Time frame: Day 1 through Day 35
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henk W Reesink, MD principal investigator
Academic Medical Centre AMC Amsterdam
Stephan Riordan principal investigator
Scientia Clinical Research Limited Sydney
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EYP001a, Entecavir and peg-interferon alfa-2a in people with Hepatitis B, Chronic, run by Enyo Pharma at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Poland, Australia, Netherlands, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Type and frequencies of adverse events (time frame: Day 1 through Day 35). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2018.