RESEARCH QUESTION/RATIONALE: Patients with chronic hepatitis B (CHB) are at risk of liver cirrhosis and -cancer. A cure is rarely achieved. Curing CHB is challenging because of the presence of a reservoir of stable covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. In a laboratory study, terbinafine, an antifungal agent, inhibits cccDNA transcription and viral replication. This pilot study will assess clinical efficacy and safety.
HYPOTHESIS: Terbinafine can inhibit cccDNA transcription in vivo, either as monotherapy or as part of combination therapy, and is safe in CHB patients.
STUDY DESIGN: Single center, randomized, double blinded, placebo-controlled, proof of concept clinical trial.
STUDY POPULATION: A) CHB patients who do not receive anti-viral treatment, and B) CHB patients who are treated with the nucleotide analogue tenofovir for > 6 months resulting in suppression of HBV DNA.
INTERVENTION (& COMPARATOR): Patients will receive (orally) 250 mg terbinafine daily (the registered dose for onchomycosis treatment) for 4 weeks, followed by a drug-pause of 2 weeks in which safety is assessed. Subsequently, patients will receive 500 mg terbinafine (orally) daily for 4 weeks.
OUTCOME MEASURES: Primary: The level of serum HBsAg, and HBV DNA (group A); Secondary: Safety based on liver-related serum markers; and viral markers: HBV-RNA, HBcrAg and HBeAg.
SAMPLE SIZE/DATA-ANALYSIS: A total of 26 patients will be included: 13 patients (11 active/ 2 placebo) per group; Data will be stored in CASTOR and analyzed by using SPSS.