HepBTer: From fungus to virus, a phase 2a clinical trial investigating the safety and efficacy of terbinafine in chronic hepatitis B patients

Lab values

• 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 rifampicine). 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

• 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.