Hepatitis B, ChronicPhase 1NCT03320616
EYP001a Food Effect Study in Subjects With Chronic Hepatitis B Virus (HBV) Infection
A Phase 1 study testing EYP001a in people with Hepatitis B, Chronic, run by Enyo Pharma at 1 site in Netherlands.
Trial summary
The farnesoid X receptor (FXR) regulates hepatitis B virus replication through the bile acids pathway. 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Feb 2017to 12 Oct 2017
- 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
- Has given voluntary written informed consent before performance of any study related procedure
- Has documented chronic HBV infection (documented within 12 months of screening visit), with criteria at screening: hepatitis B surface antigen (HBsAg) ≥ 50 IU/mL; HBV DNA > 100 IU/mL; hepatitis Be antigen (HBeAg) negative or positive
- Gender: male or female
- Age: 18-65 years, inclusive, at screening
- Body mass index (BMI): 17.0-35.0 kg/m2 inclusive, at screening
- Weight: >60 kg for males and >45 kg for females
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- Has clinical chemistry, hematology, coagulation and urinalysis tests within normal, allowable limits (with the exception of alanine aminotransferase (ALAT) [see inclusion criterion #10]); if there is an out of range value, it must be considered clinically insignificant in order to be eligible
- Has normal vital signs after at least 5 minutes resting in supine position at screening: 95 mm Hg < systolic blood pressure < 140 mm Hg; 45 mm Hg < diastolic blood pressure < 90 mm Hg; 40 bpm < heart rate < 90 bpm
- Has no clinically significant abnormal 12-lead automatic electrocardiogram (ECG) (incomplete right bundle branch block can be accepted) at screening: 120 ms < PR-interval < 210 ms, QRS-duration < 120 ms, corrected QT interval (QTc) (Fridericia's) ≤ 450 msec for males and females
- Has ALAT ≤ 3 x upper limit of normal (ULN) at screening
- Has documented liver histology with Metavir score (F0, F1, F2 or F3) or liver fibrosis documented with non-invasive alternatives to liver biopsy (Fibroscan) or shear wave elastography (Aixplorer) value < 14.6 kPa
- Agrees to abstain from all medication, including non-prescription and prescription medication (including vitamins and natural or herbal remedies, e.g. St. John's Wort) for 28 days prior to (each) admission to the clinical research center until discharge, except for authorized medications such as hormonal contraceptives for females (registered in The Netherlands) and paracetamol. On a case-by-case basis, regular co-medication either as defined on the separate medication exception list or as documented by written approval from the Sponsor and the PI as acceptable prior to randomization, will not be considered as a deviation from this criterion. All other situations related to co-medications are considered as deviations
- 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 postmenopausal [amenorrhoea duration of 12 consecutive months); non-pregnancy will be confirmed for all females by a serum pregnancy test conducted at screening and at (each) admission to the clinical research center
- 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 followup 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 (first) admission to the clinical research center 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 PI, would jeopardize the safety of the subject or impact the validity of the study results
- Willingness to abstain from alcohol and methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) from 48 hours prior to (each) admission to the clinical research center
Who cannot join
- Previous participation in the current study
- Employee of PRA or the Sponsor
- Currently receives or has received during the 60 days (or 5 half-lives of the specific drug, whichever is longer) before (first) admission to the clinical research center until (the last) discharge a nucleos(t)ide-analogue therapy or other anti HBV treatment (interferons, experimental anti HBV drugs or vaccines)
- Coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Receives or plans to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first study drug administration
- Receiving or planning to receive interferon (IFN) during the study or ≤12 months prior to the first study drug administration
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- Has significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia
- Clinical diagnosis of substance abuse with alcohol (regular alcohol consumption >21 units [men] and >14 units [women] per week [1 unit = ½ pint of beer, 25 mL shot of 40% spirit or a 125 mL glass of wine]), narcotics, or cocaine ≤12 months prior to screening
- 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 clinically significant gastrointestinal disease, especially peptic ulcerations, gastrointestinal bleeding, ulcerative colitis, cholecystectomy, Crohn's disease or Irritable Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the PI, would jeopardize the safety of the subject or impact the validity of the study results
- Has had acute diarrhea or constipation in the 7 days before (first) admission to the clinical research center. Diarrhea will be defined as the passage of liquid feces and/or a stool frequency of > 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day.
- Has a history of long QT syndrome
- Has participated in a drug study within 30 days prior to the first drug administration in the current study
- Has a positive drug and alcohol screen (opiates, methadone, cocaine, methamphetamines, amphetamines, ecstasy, barbiturates, benzodiazepines, tricyclic antidepressants, phencyclidine and alcohol)
- Any current or previous (ie, ≤12 months prior to screening) abuse of drugs such as opiates, cocaine, ecstasy, or intravenous amphetamines. Subjects who admit to occasional use of cannabis will not be excluded as long as they are able to abstain from cannabis when they are in the clinical research center.
- Has an uncontrolled current illness (e.g., active infection)
- Has had major surgery within 30 days prior to the first drug administration, or 12 months prior to the first drug administration for gastrointestinal surgery
- Has lost more than 100 mL of blood within 60 days prior to the first drug administration
- Has a history of relevant drug and/or food allergies
- Smokes more than 20 cigarettes per day
- Non-willingness to consume the Food and Drug Administration (FDA) breakfast
- Poor venous accessibility
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, Randomized, 4-Way Crossover Study in Subjects With Chronic Hepatitis B Virus Infection to Assess Pharmacokinetics (Fasted/Fed), Safety, Tolerability and Pharmacodynamics of Single Oral Doses of Farnesoid X Receptor Agonist EYP001a
The farnesoid X receptor (FXR) regulates hepatitis B virus replication through the bile acids pathway. EYP001a is a selective, synthetic FXR agonist under development for the treatment of hepatitis B.
This Phase 1 study is designed primarily to assess Pharmacokinetics (PK) under fed and fasted conditions, and to assess the safety, tolerability and Pharmacodynamics (PD) of single oral doses of EYP001a in subjects with chronic HBV infection.
Read the detailed description
This is a single-center, open-label, randomized, 4-way crossover study.
A total of 14 chronic HBV subjects will participate. Subjects will receive 4 single dose administrations of EYP001a during the study. There will be 2 separate dosing periods: 1 period with 2 single administrations of EYP001a in the morning, once under fasted conditions and once under fed condition (separated by 48.5 hours), and 1 period with 2 single administrations of EYP001a in the evening, once under fasted conditions and once under fed condition (separated by 48.5 hours).
The subjects will be randomized to 1 of 4 treatment sequences:
- Sequence 1: Period 1 first dose morning fasted, second dose morning fed; Period 2 first dose evening fasted, second dose evening fed.
- Sequence 2: Period 1 first dose evening fasted, second dose evening fed; Period 2 first dose morning fasted, second dose morning fed.
- Sequence 3: Period 1 first dose morning fed, second dose morning fasted; Period 2 first dose evening fed, second dose evening fasted.
- Sequence 4: Period 1 first dose evening fed, second dose evening fasted; Period 2 first dose morning fed, second dose morning fasted.
Participation will include an eligibility screening period of maximally 40 days, clinic stay during the treatment periods, and a followup visit 4 to 6 days after the last study drug administration.
The safety and tolerability of EYP001a will be assessed by evaluating vital signs, ECGs, liver ultrasound, clinical laboratory and adverse events.
- Conditions
- Hepatitis B, Chronic
- Being tested
- EYP001a
- 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
Oral EYP001a capsules - 100 mg strength
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Experimental | 4 single doses of EYP001a: Period 1 first dose morning fasted, second dose morning fed; Period 2 first dose evening fasted, second dose evening fed Receives: Drug: EYP001a |
| Sequence 2 | Experimental | 4 single doses of EYP001a: Period 1 first dose evening fasted, second dose evening fed; Period 2 first dose morning fasted, second dose morning fed Receives: Drug: EYP001a |
| Sequence 3 | Experimental | 4 single doses of EYP001a: Period 1 first dose morning fed, second dose morning fasted; Period 2 first dose evening fed, second dose evening fasted Receives: Drug: EYP001a |
| Sequence 4 | Experimental | 4 single doses of EYP001a: Period 1 first dose evening fed, second dose evening fasted; Period 2 first dose morning fed, second dose morning fasted Receives: Drug: EYP001a |
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 of Period 1 through Day 7 to Day 9 of Period 2
Secondary outcomes (5)
Maximum observed plasma concentration (Cmax) of EYP001a
ng/mL
Measured: Predose to 48 hours after dosing
Time to attain maximum observed plasma concentration (Tmax) after EYP001a administration
h
Measured: Predose to 48 hours after dosing
Area under the plasma concentration-time curve (AUC)
ng*h/mL
Measured: Predose to 48 hours after dosing
Bile acid precursor C4 (7α hydroxy-4-cholesten-3-one)
ng/mL
Measured: Predose to 48 hours after dosing
Bile-regulating fibroblast growth factor 19 (FGF-19)
pg/mL
Measured: Predose to 48 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2017
- Study start10 Feb 2017
- Primary completion12 Oct 2017
- Study completion12 Oct 2017
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
- Model description
- The subjects will be randomized to 1 of 4 treatment sequences.
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enyo Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Jeroen van de Wetering, MD, Principal investigator, PRA-EDS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03320616
- Sponsor's protocol ID
- EYP001-102
- Other IDs
- 2016-004713-27, 2016
- Status last verified
- Mar 2018
- First submitted
- 20 Oct 2017
- Last updated
- 5 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Randomized, 4-Way Crossover Study in Subjects With Chronic Hepatitis B Virus Infection to Assess Pharmacokinetics (Fasted/Fed), Safety, Tolerability and Pharmacodynamics of Single Oral Doses of Farnesoid X Receptor Agonist EYP001a
- ClinicalTrials.gov ID
- NCT03320616
- Acronym / sponsor ID
- EYP001-102
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Enyo PharmaIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 10 Feb 2017 (actual)
- Primary completion
- 12 Oct 2017 (actual)
- Study completion
- 12 Oct 2017 (actual)
- First posted
- 25 Oct 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.
The farnesoid X receptor (FXR) regulates hepatitis B virus replication through the bile acids pathway. EYP001a is a selective, synthetic FXR agonist under development for the treatment of hepatitis B.
This Phase 1 study is designed primarily to assess Pharmacokinetics (PK) under fed and fasted conditions, and to assess the safety, tolerability and Pharmacodynamics (PD) of single oral doses of EYP001a in subjects with chronic HBV infection.
Detailed description
This is a single-center, open-label, randomized, 4-way crossover study.
A total of 14 chronic HBV subjects will participate. Subjects will receive 4 single dose administrations of EYP001a during the study. There will be 2 separate dosing periods: 1 period with 2 single administrations of EYP001a in the morning, once under fasted conditions and once under fed condition (separated by 48.5 hours), and 1 period with 2 single administrations of EYP001a in the evening, once under fasted conditions and once under fed condition (separated by 48.5 hours).
The subjects will be randomized to 1 of 4 treatment sequences:
- Sequence 1: Period 1 first dose morning fasted, second dose morning fed; Period 2 first dose evening fasted, second dose evening fed.
- Sequence 2: Period 1 first dose evening fasted, second dose evening fed; Period 2 first dose morning fasted, second dose morning fed.
- Sequence 3: Period 1 first dose morning fed, second dose morning fasted; Period 2 first dose evening fed, second dose evening fasted.
- Sequence 4: Period 1 first dose evening fed, second dose evening fasted; Period 2 first dose morning fed, second dose morning fasted.
Participation will include an eligibility screening period of maximally 40 days, clinic stay during the treatment periods, and a followup visit 4 to 6 days after the last study drug administration.
The safety and tolerability of EYP001a will be assessed by evaluating vital signs, ECGs, liver ultrasound, clinical laboratory and adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The subjects will be randomized to 1 of 4 treatment sequences.
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Drug: EYP001a4 single doses of EYP001a: Period 1 first dose morning fasted, second dose morning fed; Period 2 first dose evening fasted, second dose evening fed |
| Sequence 2 | Experimental | Drug: EYP001a4 single doses of EYP001a: Period 1 first dose evening fasted, second dose evening fed; Period 2 first dose morning fasted, second dose morning fed |
| Sequence 3 | Experimental | Drug: EYP001a4 single doses of EYP001a: Period 1 first dose morning fed, second dose morning fasted; Period 2 first dose evening fed, second dose evening fasted |
| Sequence 4 | Experimental | Drug: EYP001a4 single doses of EYP001a: Period 1 first dose evening fed, second dose evening fasted; Period 2 first dose morning fed, second dose morning fasted |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Has given voluntary written informed consent before performance of any study related procedure
- Has documented chronic HBV infection (documented within 12 months of screening visit), with criteria at screening: hepatitis B surface antigen (HBsAg) ≥ 50 IU/mL; HBV DNA > 100 IU/mL; hepatitis Be antigen (HBeAg) negative or positive
- Gender: male or female
- Age: 18-65 years, inclusive, at screening
- Body mass index (BMI): 17.0-35.0 kg/m2 inclusive, at screening
Key exclusion criteria (22 listed)
- Previous participation in the current study
- Employee of PRA or the Sponsor
- Currently receives or has received during the 60 days (or 5 half-lives of the specific drug, whichever is longer) before (first) admission to the clinical research center until (the last) discharge a nucleos(t)ide-analogue therapy or other anti HBV treatment (interferons, experimental anti HBV drugs or vaccines)
- Coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Receives or plans to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first study drug administration
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 |
|---|---|---|
| EYP001aOral EYP001a capsules - 100 mg strength | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
Primary outcome
Type and frequencies of adverse events
Time frame: Day 1 of Period 1 through Day 7 to Day 9 of Period 2
5 secondary outcomes
Maximum observed plasma concentration (Cmax) of EYP001a
Time frame: Predose to 48 hours after dosing
Time to attain maximum observed plasma concentration (Tmax) after EYP001a administration
Time frame: Predose to 48 hours after dosing
Area under the plasma concentration-time curve (AUC)
Time frame: Predose to 48 hours after dosing
Bile acid precursor C4 (7α hydroxy-4-cholesten-3-one)
Time frame: Predose to 48 hours after dosing
Bile-regulating fibroblast growth factor 19 (FGF-19)
Time frame: Predose to 48 hours after dosing
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 5 Mar 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.
Jeroen van de Wetering, MD principal investigator
PRA-EDS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EYP001a in people with Hepatitis B, Chronic, run by Enyo Pharma at 1 site in Netherlands.
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 17 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 5 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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. 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 of Period 1 through Day 7 to Day 9 of Period 2). 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 5 Mar 2018.