From Fungus to Virus, Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients

From Fungus to Virus, a Phase 1b Clinical Trial Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients

From Fungus to Virus, Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients (NCT06295328) is a Phase 1 / Phase 2 interventional studying Chronic Hepatitis b, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Chronic Hepatitis b, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 36 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age 18 - 60 years 2. Proven CHB for more than 6 months, based on serology (HBsAg positivity) and at screening a viral load of: i) Group A: HBV DNA ≥200 IU/mL and \<20,000 IU/mL ii) Group B: HBV DNA \< 20 IU/mL 3. HBeAg-positive or HBeAg-negative 4. No current use of any antiviral medication (group A) or currently treated with tenofovir only, for \> 6 months (group B). 5. Normal liver function tests, assessed as follows: i) 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) 6. Body mass index (BMI): 17.0-35.0 kg/m2 7. Clinical chemistry, hematologic and coagulation tests at screening must be within normal limits or clinically non-significant, as by the investigator's assessment. 8. 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. 9. 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. 10. 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. 11. Written willing to sign a consent form must be obtained before any study related interventions (including screening and enrollment) can be conducted. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Age 18 - 60 years 2. Proven CHB for more than 6 months, based on serology (HBsAg positivity) and at screening a viral load of: i) Group A: HBV DNA ≥200 IU/mL and \<20,000 IU/mL ii) Group B: HBV DNA \< 20 IU/mL 3. HBeAg-positive or HBeAg-negative 4. No current use of any antiviral medication (group A) or currently treated with tenofovir only, for \> 6 months (group B). 5. Normal liver function tests, assessed as follows: i) 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) 6. Body mass index (BMI): 17.0-35.0 kg/m2 7. Clinical chemistry, hematologic and coagulation tests at screening must be within normal limits or clinically non-significant, as by the investigator's assessment. 8. 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. 9. 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. 10. 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. 11. Written informed consent must be obtained before any study related interventions (including screening and enrollment) can be conducted. Exclusion Criteria: 1. Currently active, or a history of liver cirrhosis determined by one or more of the following: i) Liver biopsy; ii) Elastography (e.g. Fibroscan); iii) Combination of usual radiological and biochemical criteria 2. Currently active liver disease other than CHB 3. Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV) and/or human immunodeficiency virus (HIV) 4. Acute hepatitis A virus (HAV) infection at screening 5. Renal impairment (estimated glomerular filtration rate (eGRF) \< 60ml/min) 6. Currently active, or a history of, psoriasis or lupus erythematodes 7. 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). 8. 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. 9. 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. 10. 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 \[women\]) 11. Inability to understand the patient information and make an informed decision to participate

Treatments Being Tested

DRUG

Terbinafine

terbinafine 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid.

DRUG

Placebo

Placebo 250mg once daily for 4 weeks, followed by 2 weeks washout, followed by 4 weeks bid.

DRUG

Tenofovir

Tenofovir 245mg standard of care

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Amsterdam UMC

Amsterdam, North Holland, Netherlands

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06295328), the sponsor (Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06295328 clinical trial studying?

Who can participate in NCT06295328?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06295328?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06295328. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06295328. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.