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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
51
Number of placebo tablets administered orally depends on the arm
Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm
National University Hospital
Singapore, Singapore
Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline
Time frame: Baseline to 12 weeks
Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment
Proportion of participants with sustained HBsAg loss with suppression of HBV DNA for 24 weeks after the end of treatment
Time frame: Baseline to 24 weeks after the end of treatment
Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment
Change in mean Quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline to Day 3, Week 1, Week 2, Week 4, and Week 8
Time frame: 8 weeks
Hepatitis B Surface Antigen (HBsAg) Loss
Proportion of participants with HBsAg loss defined as quantitative HBsAg below the lower limit of quantitation at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12
Time frame: 12 weeks
Hepatitis B Surface Antigen (HBsAg) Seroconversion
Proportion of participants with hepatitis B surface antigen (HBsAg) seroconversion defined as HBsAg loss and gain of anti-hepatitis B antibodies at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12
Time frame: 12 weeks
Hepatitis B Virus DNA Suppression
Proportion of participants with hepatitis B virus DNA suppression defined as hepatitis B virus DNA below the lower limit of quantitation (20 IU/mL) at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12
Time frame: 12 weeks
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Change in Fibrosis-4 (FIB-4) Score
Mean change in Fibrosis-4 (FIB-4) score from Baseline to Week 1, Week 2, Week 4, Week 8, and Week 12. FIB-4 score is calculated as (age in years \* Aspartate aminotransferase (AST) in U/L)/(platelet count in 10\^9 U/L \* square root of alanine aminotransferase (ALT) in U/L). FIB-4 scores under 1.45 have a negative predictive value of 90% for advanced fibrosis (better outcome) and FIB-4 scores \>3.25 have a positive predictive value of 65% for advanced fibrosis (worse outcome). See Sterling RK, Lissen E, Clumeck N, et. al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology 2006;43:1317-1325.
Time frame: 12 weeks
Change in FibroScan Score
Mean change in FibroScan score from Baseline to end of treatment. Fibroscan is a kind of liver elastography measuring liver stiffness in kilopascals (kPa). Higher results are consistent with liver disease (worse outcome).
Time frame: Baseline to end of treatment