Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Placebo Oral Tablet; Nitazoxanide
Intervention description: Number of placebo tablets administered orally depends on the arm; Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm
Intervention MeSH terms: Nitazoxanide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients are randomized 1:1:1:1 (12 subjects per group)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 51.0
Sex: All
Minimum age: 21 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      This randomized controlled trial is designed to evaluate safety, effectiveness and
      pharmacokinetic-pharmacodynamic (PK/PD) relationships associated with three different
      Nitazoxanide (NTZ) treatment regimens added to Tenofovir Disoproxil Fumarate (TDF), Tenofovir
      Alafenamide (TAF) or Entecavir (ETV) in treating Chronic Hepatitis B (CHB).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age at least 21 years

          2. 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))

          3. Hepatitis B e Antigen (HBeAg) negative

          4. 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

          5. Quantitative HBsAg greater than 100 IU/mL

          6. Alanine Aminotransferase (ALT) below 1.5 times the upper limit of normal

          7. Able to comply with the study requirements

        Exclusion Criteria:

          1. Unable to take oral medications

          2. 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.

          3. Any investigational drug therapy within 30 days prior to enrollment

          4. Other causes of liver disease

          5. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or
             hepatitis D virus (HDV) based on an enzyme immunoassay (EIA)

          6. History of alcoholism or with an alcohol consumption of greater than 40 g per day

          7. Clinically unstable

          8. 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

          9. History of hypersensitivity or intolerance to NTZ or any of the excipients comprising
             the NTZ tablets

         10. Hepatocellular carcinoma

         11. Decompensated liver disease including history of ascites, bleeding esophageal varices,
             portal hypertension or hepatic encephalopathy

         12. FibroScan® score greater than 11 or history of cirrhosis on liver biopsy

         13. Creatinine clearance <65 ml/minute (by the Cockcroft-Gault equation using ideal body
             weight)

         14. 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

         15. Malignant disease within 3 years of trial entry

         16. Rheumatological conditions, inflammatory bowel disease or psoriasis requiring or
             anticipated to require biological/immunosuppressive therapies

         17. Subjects taking or anticipated to need medications considered to be major CYP2C8
             substrates