Chronic Hepatitis bPhase 1/2HepBTerNCT06295328
From Fungus to Virus, Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients
A Phase 1/2 study testing Terbinafine and Tenofovir in people with Chronic Hepatitis b, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Rationale: Currently, there is no curative therapy available for patients that are chronically infected with the hepatitis B virus (HBV). Especially the presence of a viral reservoir of stable episomal, covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes poses a great challenge for the… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Hepatitis b
- What is being tested?
- Terbinafine and Tenofovir
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteNetherlands
- Study dates
- 13 Apr 2022to 1 Apr 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18 - 60 years
- Proven CHB for more than 6 months, based on serology (HBsAg positivity) and at screening a viral load of:
- Group A: HBV DNA ≥200 IU/mL and <20,000 IU/mL ii) Group B: HBV DNA < 20 IU/mL
- HBeAg-positive or HBeAg-negative
- No current use of any antiviral medication (group A) or currently treated with tenofovir only, for > 6 months (group B).
- Normal liver function tests, assessed as follows:
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- Liver stiffness measurement using Fibroscan® of ≤ 7.0 kiloPascal (kPa) ii) Alanine aminotransferase (ALT) and/or aspirate aminotransferase (AST) at screening ≤ 1.25 x upper limit of normal (ULN) iii) Thrombocytes 150-400 10E9/L iv) Total bilirubin 0-17 µmol/L (elevated levels may be accepted if unconjugated portion is elevated in patients with Gilbert syndrome) v) Albumin within normal value (35 - 50 g/L) vi) Prothrombin Time (PT) within normal value (9,5 - 12.5 sec) vii) Alkaline phosphatase (ALP) and Gamma-glutamyltransferase (GGT) within normal values (40-120 U/L and 0-40 U/L respectively)
- Body mass index (BMI): 17.0-35.0 kg/m2
- Clinical chemistry, hematologic and coagulation tests at screening must be within normal limits or clinically non-significant, as by the investigator's assessment.
- At screening, women of child bearing potential must be non-pregnant and non-lactating; a urine or serum pregnancy test will be performed at screening.
- Female patients of child-bearing potential (with a fertile male sexual partner) and male patients (if not surgically sterilized) must be willing to use adequate contraception from screening until last study visit.
- No recent (<3 months) history of any clinically significant conditions, which, in the opinion of the investigator, would jeopardize the safety of the patient or impact the validity of the study results.
- Written informed consent must be obtained before any study related interventions (including screening and enrollment) can be conducted.
Who cannot join
- Currently active, or a history of liver cirrhosis determined by one or more of the following:
- Liver biopsy; ii) Elastography (e.g. Fibroscan); iii) Combination of usual radiological and biochemical criteria
- Currently active liver disease other than CHB
- Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV) and/or human immunodeficiency virus (HIV)
- Acute hepatitis A virus (HAV) infection at screening
- Renal impairment (estimated glomerular filtration rate (eGRF) < 60ml/min)
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- Currently active, or a history of, psoriasis or lupus erythematodes
- Use of oral medication that interacts with the liver metabolism enzyme CYP2D6, or which is known to be hepatotoxic or otherwise known to interact with terbinafine (such as rifampicin).
- The use of a L-type calcium (LTCC) blocker (such as lomerizine of nifedipine), since these may interact with the HBV transcription according to the article by Klundert et al.
- Usage or plans to receive systemic immunosuppressive or immunomodulating medication (e.g. IFN) during the study or ≤4 months prior to the first investigational product administration.
- Clinical diagnosis of substance abuse ≤12 months prior to screening with narcotics or cocaine or with alcohol (regular consumption >14 units/week [men] and >7 units/week [women])
- Inability to understand the patient information and make an informed decision to participate
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105AZ
M.W. Peters, RN, +31207320393, m.w.peters@amsterdamumc.nl
D.J. van Doorn, MD
About this study
Official title: From Fungus to Virus, a Phase 1b Clinical Trial Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients
Rationale: Currently, there is no curative therapy available for patients that are chronically infected with the hepatitis B virus (HBV). Especially the presence of a viral reservoir of stable episomal, covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes poses a great challenge for the development of curative therapies. HBV cccDNA acts as the template for production of viral proteins and HBV genomes. In a preclinical study, terbinafine (an antifungal agent) was identified as a potent and specific suppressor of HBx-mediated cccDNA transcription. HBx is an accessory viral protein of HBV which has been proven to be essential for HBV replication and enhances replication at the transcriptional level in vivo. The suppression of cccDNA transcription results in a strong reduction of the production of viral genomes (RNA and DNA) as well as viral proteins. This will allow recovery of the immune system, increase viral clearance and prevent replenishment of the cccDNA pool in the hepatocyte, all contributing to cure chronic hepatitis B (CHB).
Objective: to provide proof of concept for the inhibition of HBx mediated cccDNA transcription by terbinafine, both as monotherapy and add-on therapy next to tenofovir. Secondary outcomes will be the safety and tolerability of terbinafine in this specific group.
Read more
Study design: This pilot study is a stratified, single center, randomized, double-blinded, placebo-controlled, dose-ascending proof of concept clinical trial.
Study population: patients chronically infected with the hepatitis B virus with a normal liver function and no signs of liver damage, who do not use any antiviral medication (group A, n=16) or are treated with tenofovir > 6 months (group B, n=16).
Intervention: Patients will be randomly allocated to daily oral treatment with terbinafine or a matched placebo, either as monotherapy (group A) or as add-on therapy to tenofovir (group B).
Main study parameters/endpoints: Primary outcomes: decline in level of serum HBsAg >0.32log10 IU/mL in both groups A and B and decline in serum HBV DNA >0.86log10 in group A at the end of study treatment (week 10 vs baseline). Secondary outcomes: 1) Safety and tolerability of terbinafine as mono- or combination therapy; 2) level of serum HBsAg and HBV DNA at 3 months follow-up; 3) decline of HBsAg levels over time (all visits); 4) HBV RNA, large HBsAg (LHBs) HBcrAg levels, and HBeAg status at baseline and end of study 4).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients participating in this study will undergo physical examinations and blood sample collections (13 samples and in total 467.5 mL). They will also be asked to fill in the HBQOL and EQ5D5L quality of life questionnaires and a medicine diary. In total there will be 13 visits in the hospital of which 7 will be for blood collection only. Terbinafine can induce liver damage 1 of 50,000 to 120,000 prescriptions (LiverTox), a weekly safety laboratory control is implemented in the visits to detect possible liver toxicity in an early stage and prevent liver damage.
- Conditions
- Chronic Hepatitis b
- Being tested
- Terbinafine, Placebo, Tenofovir
- 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.
TerbinafineDrug
terbinafine 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid.
PlaceboDrug
Placebo 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid.
TenofovirDrug
Tenofovir 245mg standard of care
| Study group | Role | What they receive |
|---|---|---|
| NUC + Study drug | Active comparator | Tenofovir + Terbinafine Receives: Drug: Terbinafine; Drug: Tenofovir |
| NUC + Placebo | Placebo comparator | Tenofovir + Placebo Receives: Drug: Placebo; Drug: Tenofovir |
| Study drug | Active comparator | Terbinafine Receives: Drug: Terbinafine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in level of serum HBsAG
- Change in level of serum HBsAg >0.32 log10 IU/mL at the end of study treatment (week 10 vs baseline).
Measured: 10 weeks
Change in serum HBV DNA
- Change in serum HBV DNA >0.86 log10 in group A (monotherapy) at the end of study treatment (week 10 vs baseline).
Measured: 10 weeks
Secondary outcomes (6)
Safety of terbinafine
- Safety of terbinafine as mono- or combination therapy, as defined by the number of patients with treatment-related laboratory adverse events as assessed by CTCAE v4.0.
Measured: 10 weeks
Tolerability of terbinafine
- Tolerability of terbinafine as mono- or combination therapy, as defined by the number of patients with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 10 weeks
Serum levels of HBsAG
- Level of serum (large) HBsAg at 3 months follow-up.
Measured: 3 months
Serum levels of HBV DNA
- Level of serum HBV DNA at 3 months follow-up.
Measured: 3 months
Serum levels of HBV RNA
- Level of serum HBV RNA at 3 months follow-up.
Measured: 3 months
Serum levels of HBcrAg
- Level of serum HBcrAg at 3 months follow-up.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2024
- Study start13 Apr 2022
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis bStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1b study with two parallel treatment arms and placebo controls.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ulrich Beuers, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06295328
- Sponsor's protocol ID
- NL 72439.018.19
- Acronym
- HepBTer
- Status last verified
- Feb 2025
- First submitted
- 12 Feb 2024
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From Fungus to Virus, a Phase 1b Clinical Trial Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients
- ClinicalTrials.gov ID
- NCT06295328
- Acronym / sponsor ID
- HepBTer / NL 72439.018.19
- Conditions
- Chronic Hepatitis b
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 13 Apr 2022 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2025 (estimated)
- First posted
- 6 Mar 2024 (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.
Rationale: Currently, there is no curative therapy available for patients that are chronically infected with the hepatitis B virus (HBV). Especially the presence of a viral reservoir of stable episomal, covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes poses a great challenge for the development of curative therapies. HBV cccDNA acts as the template for production of viral proteins and HBV genomes. In a preclinical study, terbinafine (an antifungal agent) was identified as a potent and specific suppressor of HBx-mediated cccDNA transcription. HBx is an accessory viral protein of HBV which has been proven to be essential for HBV replication and enhances replication at the transcriptional level in vivo. The suppression of cccDNA transcription results in a strong reduction of the production of viral genomes (RNA and DNA) as well as viral proteins. This will allow recovery of the immune system, increase viral clearance and prevent replenishment of the cccDNA pool in the hepatocyte, all contributing to cure chronic hepatitis B (CHB).
Objective: to provide proof of concept for the inhibition of HBx mediated cccDNA transcription by terbinafine, both as monotherapy and add-on therapy next to tenofovir. Secondary outcomes will be the safety and tolerability of terbinafine in this specific group.
Study design: This pilot study is a stratified, single center, randomized, double-blinded, placebo-controlled, dose-ascending proof of concept clinical trial.
Study population: patients chronically infected with the hepatitis B virus with a normal liver function and no signs of liver damage, who do not use any antiviral medication (group A, n=16) or are treated with tenofovir > 6 months (group B, n=16).
Intervention: Patients will be randomly allocated to daily oral treatment with terbinafine or a matched placebo, either as monotherapy (group A) or as add-on therapy to tenofovir (group B).
Main study parameters/endpoints: Primary outcomes: decline in level of serum HBsAg >0.32log10 IU/mL in both groups A and B and decline in serum HBV DNA >0.86log10 in group A at the end of study treatment (week 10 vs baseline). Secondary outcomes: 1) Safety and tolerability of terbinafine as mono- or combination therapy; 2) level of serum HBsAg and HBV DNA at 3 months follow-up; 3) decline of HBsAg levels over time (all visits); 4) HBV RNA, large HBsAg (LHBs) HBcrAg levels, and HBeAg status at baseline and end of study 4).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients participating in this study will undergo physical examinations and blood sample collections (13 samples and in total 467.5 mL). They will also be asked to fill in the HBQOL and EQ5D5L quality of life questionnaires and a medicine diary. In total there will be 13 visits in the hospital of which 7 will be for blood collection only. Terbinafine can induce liver damage 1 of 50,000 to 120,000 prescriptions (LiverTox), a weekly safety laboratory control is implemented in the visits to detect possible liver toxicity in an early stage and prevent liver damage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Phase 1b study with two parallel treatment arms and placebo controls.
| Arm | Type | Receives |
|---|---|---|
| NUC + Study drug | Active comparator | Drug: Terbinafine, Drug: TenofovirTenofovir + Terbinafine |
| NUC + Placebo | Placebo comparator | Drug: Placebo, Drug: TenofovirTenofovir + Placebo |
| Study drug | Active comparator | Drug: TerbinafineTerbinafine |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Age 18 - 60 years
- Proven CHB for more than 6 months, based on serology (HBsAg positivity) and at screening a viral load of:
- HBeAg-positive or HBeAg-negative
- No current use of any antiviral medication (group A) or currently treated with tenofovir only, for > 6 months (group B).
- Normal liver function tests, assessed as follows:
Key exclusion criteria (12 listed)
- Currently active, or a history of liver cirrhosis determined by one or more of the following:
- Currently active liver disease other than CHB
- Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV) and/or human immunodeficiency virus (HIV)
- Acute hepatitis A virus (HAV) infection at screening
- Renal impairment (estimated glomerular filtration rate (eGRF) < 60ml/min)
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 |
|---|---|---|
| Terbinafineterbinafine 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid. | Drug | NUC + Study drug, Study drug |
| PlaceboPlacebo 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid. | Drug | NUC + Placebo, Placebo |
| TenofovirTenofovir 245mg standard of care | Drug | NUC + Placebo, NUC + Study drug |
Primary outcome
Change in level of serum HBsAG
Time frame: 10 weeks
- Change in level of serum HBsAg >0.32 log10 IU/mL at the end of study treatment (week 10 vs baseline).
Change in serum HBV DNA
Time frame: 10 weeks
- Change in serum HBV DNA >0.86 log10 in group A (monotherapy) at the end of study treatment (week 10 vs baseline).
6 secondary outcomes
Safety of terbinafine
Time frame: 10 weeks
Tolerability of terbinafine
Time frame: 10 weeks
Serum levels of HBsAG
Time frame: 3 months
Serum levels of HBV DNA
Time frame: 3 months
Serum levels of HBV RNA
Time frame: 3 months
Serum levels of HBcrAg
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Terbinafine and Tenofovir in people with Chronic Hepatitis b, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) 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 13 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 7 Feb 2025. 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. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact U. Beuers, Prof. Dr. (+31205662422, u.h.beuers@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in level of serum HBsAG (time frame: 10 weeks). The study lists 2 primary outcomes in all. 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 7 Feb 2025.