Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B

Inclusion criteria

• Age at least 21 years
• CHB virus infection (serum HBsAg-positive for at least 6 months or serum HBsAg-positive and negative immunoglobulin M (IgM) antibodies to Hepatitis B Virus (HBV) core antigen (IgM anti-HBc))
• Hepatitis B e Antigen (HBeAg) negative
• Virologically suppressed (HBV DNA less than the lower limit of quantitation) for at least 12 months on Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF) or Entecavir (ETV) therapy
• Quantitative HBsAg greater than 100 IU/mL
• Alanine Aminotransferase (ALT) below 1.5 times the upper limit of normal
• Able to comply with the study requirements

Exclusion criteria

• Unable to take oral medications
• Females who are pregnant, breast-feeding or not using birth control. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an intrauterine device (IUD), or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. In addition, female subjects should have a baseline pregnancy test and should agree to continue an acceptable method of birth control for the duration of the study (including follow-up) if sexually active.
• Any investigational drug therapy within 30 days prior to enrollment
• Other causes of liver disease
• Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) based on an enzyme immunoassay (EIA)
• History of alcoholism or with an alcohol consumption of greater than 40 g per day
• Clinically unstable
• Any concomitant condition that, in the opinion of the investigator would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed
• History of hypersensitivity or intolerance to NTZ or any of the excipients comprising the NTZ tablets
• Hepatocellular carcinoma
• Decompensated liver disease including history of ascites, bleeding esophageal varices, portal hypertension or hepatic encephalopathy
• FibroScan® score greater than 11 or history of cirrhosis on liver biopsy
• Creatinine clearance <65 ml/minute (by the Cockcroft-Gault equation using ideal body weight)
• History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, pathologic bone fracture or other risk factors for osteoporosis, hematological disease or medical illness that in the investigator's opinion might interfere with therapy
• Malignant disease within 3 years of trial entry
• Rheumatological conditions, inflammatory bowel disease or psoriasis requiring or anticipated to require biological/immunosuppressive therapies
• Subjects taking or anticipated to need medications considered to be major CYP2C8 substrates