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

Inclusion criteria

• Age 18 - 60 years
• 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

• 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:

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)

• 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.

Exclusion criteria

• 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

• 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)
• 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