Chronic Hepatitis B
Conditions
Brief 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).
Interventions
DRUGPlacebo Oral Tablet
Number of placebo tablets administered orally depends on the arm
DRUGNitazoxanide
Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm
Sponsors
Romark Laboratories L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Patients are randomized 1:1:1:1 (12 subjects per group)
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) | Baseline to 12 weeks | Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | 8 weeks | Change in mean Quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline to Day 3, Week 1, Week 2, Week 4, and Week 8 |
| Hepatitis B Surface Antigen (HBsAg) Loss | 12 weeks | 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 |
| Hepatitis B Surface Antigen (HBsAg) Seroconversion | 12 weeks | 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 |
| Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment | Baseline to 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 |
| Change in Fibrosis-4 (FIB-4) Score | 12 weeks | 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. |
| Change in FibroScan Score | Baseline to end of treatment | 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). |
| Hepatitis B Virus DNA Suppression | 12 weeks | 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 |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Placebo Oral Tablet: Number of placebo tablets administered orally depends on the arm | 13 |
| Group 2 Two 300 mg NTZ tablets and one placebo tablet administered orally in the morning and three placebo tablets in the evening in addition to continuing TDF, TAF or ETV therapy
Placebo Oral Tablet: Number of placebo tablets administered orally depends on the arm
Nitazoxanide: Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm | 13 |
| Group 3 Two 300 mg NTZ tablets and one placebo tablet administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Placebo Oral Tablet: Number of placebo tablets administered orally depends on the arm
Nitazoxanide: Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm | 11 |
| Group 4 Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Nitazoxanide: Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm | 14 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 9.23 | 52.7 years STANDARD_DEVIATION 9.17 | 47.7 years STANDARD_DEVIATION 7.24 | 52.0 years STANDARD_DEVIATION 10.35 | 49.8 years STANDARD_DEVIATION 9.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 13 Participants | 9 Participants | 14 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Quantitative HBsAg | 3.1 log10 IU/mL STANDARD_DEVIATION 0.5 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.45 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.34 | 2.8 log10 IU/mL STANDARD_DEVIATION 0.51 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 13 Participants | 11 Participants | 14 Participants | 51 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 13 participants | 13 participants | 11 participants | 14 participants | 51 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 10 Participants | 14 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 11 | 1 / 14 |
| other Total, other adverse events | 10 / 13 | 10 / 13 | 11 / 11 | 13 / 14 |
| serious Total, serious adverse events | 1 / 13 | 0 / 13 | 0 / 11 | 1 / 14 |
Outcome results
Primary
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
Population: All subjects who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) | 0.0 log10 IU/mL | Standard Deviation 0.13 |
| Group 2 | Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) | 0.0 log10 IU/mL | Standard Deviation 0.9 |
| Group 3 | Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) | 0.0 log10 IU/mL | Standard Deviation 0.06 |
| Group 4 | Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) | 0.0 log10 IU/mL | Standard Deviation 0.1 |
p-value: 1t-test, 2 sided
p-value: 1t-test, 2 sided
p-value: 1t-test, 2 sided
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change in FibroScan Score | 0.0 kilopascals (kPa) | Standard Deviation 1.41 |
| Group 2 | Change in FibroScan Score | 2.0 kilopascals (kPa) | Standard Deviation 1.73 |
| Group 3 | Change in FibroScan Score | 0.0 kilopascals (kPa) | Standard Deviation 0.82 |
| Group 4 | Change in FibroScan Score | 1.3 kilopascals (kPa) | Standard Deviation 1.53 |
p-value: 0.123t-test, 2 sided
p-value: 1t-test, 2 sided
p-value: 0.266t-test, 2 sided
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Change in Fibrosis-4 (FIB-4) Score | Week 8 | -1.7 FIB-4 Score | Standard Deviation 1 |
| Group 1 | Change in Fibrosis-4 (FIB-4) Score | Week 2 | -1.4 FIB-4 Score | Standard Deviation 1.08 |
| Group 1 | Change in Fibrosis-4 (FIB-4) Score | Week 12 | 0.0 FIB-4 Score | Standard Deviation 0.57 |
| Group 1 | Change in Fibrosis-4 (FIB-4) Score | Week 4 | -1.7 FIB-4 Score | Standard Deviation 0.88 |
| Group 1 | Change in Fibrosis-4 (FIB-4) Score | Week 1 | -1.7 FIB-4 Score | Standard Deviation 0.88 |
| Group 2 | Change in Fibrosis-4 (FIB-4) Score | Week 4 | -2.9 FIB-4 Score | Standard Deviation 1.03 |
| Group 2 | Change in Fibrosis-4 (FIB-4) Score | Week 8 | -2.9 FIB-4 Score | Standard Deviation 1.05 |
| Group 2 | Change in Fibrosis-4 (FIB-4) Score | Week 12 | -1.2 FIB-4 Score | Standard Deviation 1.06 |
| Group 2 | Change in Fibrosis-4 (FIB-4) Score | Week 2 | -2.8 FIB-4 Score | Standard Deviation 1.06 |
| Group 2 | Change in Fibrosis-4 (FIB-4) Score | Week 1 | -2.8 FIB-4 Score | Standard Deviation 0.97 |
| Group 3 | Change in Fibrosis-4 (FIB-4) Score | Week 4 | -2.9 FIB-4 Score | Standard Deviation 2.81 |
| Group 3 | Change in Fibrosis-4 (FIB-4) Score | Week 1 | -2.9 FIB-4 Score | Standard Deviation 2.68 |
| Group 3 | Change in Fibrosis-4 (FIB-4) Score | Week 2 | -2.9 FIB-4 Score | Standard Deviation 2.61 |
| Group 3 | Change in Fibrosis-4 (FIB-4) Score | Week 8 | -2.8 FIB-4 Score | Standard Deviation 2.67 |
| Group 3 | Change in Fibrosis-4 (FIB-4) Score | Week 12 | -1.0 FIB-4 Score | Standard Deviation 1.51 |
| Group 4 | Change in Fibrosis-4 (FIB-4) Score | Week 8 | -2.1 FIB-4 Score | Standard Deviation 0.91 |
| Group 4 | Change in Fibrosis-4 (FIB-4) Score | Week 2 | -1.8 FIB-4 Score | Standard Deviation 0.88 |
| Group 4 | Change in Fibrosis-4 (FIB-4) Score | Week 1 | -2.0 FIB-4 Score | Standard Deviation 0.86 |
| Group 4 | Change in Fibrosis-4 (FIB-4) Score | Week 4 | -1.8 FIB-4 Score | Standard Deviation 1.07 |
| Group 4 | Change in Fibrosis-4 (FIB-4) Score | Week 12 | -0.8 FIB-4 Score | Standard Deviation 0.76 |
Comparison: Comparison of Week 1 valuesp-value: 0.006t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: 0.003t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 0.004t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 0.006t-test, 2 sided
Comparison: Comparison of Week 12 valuesp-value: 0.002t-test, 2 sided
Comparison: Comparison of Week 1 valuesp-value: 0.141t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: 0.081t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 0.16t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 0.184t-test, 2 sided
Comparison: Comparison of Week 12 valuesp-value: 0.046t-test, 2 sided
Comparison: Comparison of Week 1 valuesp-value: 0.379t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: 0.308t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 0.794t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 0.297t-test, 2 sided
Comparison: Comparison of Week 12 valuesp-value: 0.007t-test, 2 sided
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 4 | 0.0 log10 IU/mL | Standard Deviation 0.08 |
| Group 1 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 1 | 0.0 log10 IU/mL | Standard Deviation 0.06 |
| Group 1 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 8 | 0.0 log10 IU/mL | Standard Deviation 0.06 |
| Group 1 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 2 | 0.0 log10 IU/mL | Standard Deviation 0.05 |
| Group 1 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Day 3 | 0.0 log10 IU/mL | Standard Deviation 0.04 |
| Group 2 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 2 | 0.0 log10 IU/mL | Standard Deviation 0.11 |
| Group 2 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 4 | 0.0 log10 IU/mL | Standard Deviation 0.09 |
| Group 2 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 8 | 0.0 log10 IU/mL | Standard Deviation 0.14 |
| Group 2 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 1 | 0.0 log10 IU/mL | Standard Deviation 0.05 |
| Group 2 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Day 3 | 0.0 log10 IU/mL | Standard Deviation 0.08 |
| Group 3 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 2 | 0.0 log10 IU/mL | Standard Deviation 0.04 |
| Group 3 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Day 3 | 0.0 log10 IU/mL | Standard Deviation 0.04 |
| Group 3 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 1 | 0.0 log10 IU/mL | Standard Deviation 0.04 |
| Group 3 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 4 | 0.0 log10 IU/mL | Standard Deviation 0.05 |
| Group 3 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 8 | -0.1 log10 IU/mL | Standard Deviation 0.07 |
| Group 4 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 4 | 0.1 log10 IU/mL | Standard Deviation 0.07 |
| Group 4 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 1 | 0.0 log10 IU/mL | Standard Deviation 0.05 |
| Group 4 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Day 3 | 0.0 log10 IU/mL | Standard Deviation 0.06 |
| Group 4 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 2 | 0.1 log10 IU/mL | Standard Deviation 0.05 |
| Group 4 | Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment | Week 8 | 0.0 log10 IU/mL | Standard Deviation 0.1 |
Comparison: Comparison of Day 3 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 1 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Day 3 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 1 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 0.001t-test, 2 sided
Comparison: Comparison of Day 3 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 1 valuesp-value: 1t-test, 2 sided
Comparison: Comparison of Week 2 valuesp-value: <0.001t-test, 2 sided
Comparison: Comparison of Week 4 valuesp-value: 0.002t-test, 2 sided
Comparison: Comparison of Week 8 valuesp-value: 1t-test, 2 sided
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 1 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 12 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Day 3 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 8 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 4 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 2 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 8 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 12 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 1 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 2 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 4 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Loss | Day 3 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 12 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Day 3 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 4 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 8 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 2 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 1 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 12 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Day 3 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 2 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 4 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 8 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Loss | Week 1 | 0 Participants |
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Day 3 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 1 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 2 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 4 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 8 | 0 Participants |
| Group 1 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 12 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 12 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 4 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Day 3 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 2 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 1 | 0 Participants |
| Group 2 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 8 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 1 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 2 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 4 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 12 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 8 | 0 Participants |
| Group 3 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Day 3 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 8 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 12 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 1 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 4 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Day 3 | 0 Participants |
| Group 4 | Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 2 | 0 Participants |
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Hepatitis B Virus DNA Suppression | Day 3 | 13 Participants |
| Group 1 | Hepatitis B Virus DNA Suppression | Week 1 | 13 Participants |
| Group 1 | Hepatitis B Virus DNA Suppression | Week 2 | 13 Participants |
| Group 1 | Hepatitis B Virus DNA Suppression | Week 4 | 13 Participants |
| Group 1 | Hepatitis B Virus DNA Suppression | Week 8 | 13 Participants |
| Group 1 | Hepatitis B Virus DNA Suppression | Week 12 | 13 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Week 12 | 13 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Week 4 | 12 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Day 3 | 13 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Week 2 | 12 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Week 1 | 12 Participants |
| Group 2 | Hepatitis B Virus DNA Suppression | Week 8 | 12 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Week 1 | 11 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Week 2 | 11 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Week 4 | 11 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Week 12 | 11 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Week 8 | 11 Participants |
| Group 3 | Hepatitis B Virus DNA Suppression | Day 3 | 11 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Week 8 | 14 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Week 12 | 13 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Week 1 | 14 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Week 4 | 13 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Day 3 | 13 Participants |
| Group 4 | Hepatitis B Virus DNA Suppression | Week 2 | 13 Participants |
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Comparison: Comparison of Day 3 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 1 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 2 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 4 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 8 valuesp-value: 1Fisher Exact
Comparison: Comparison of Week 12 valuesp-value: 1Fisher Exact
Secondary
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
Population: All participants who received at least one dose of study medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment | 0 Participants |
| Group 2 | Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment | 0 Participants |
| Group 3 | Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment | 0 Participants |
| Group 4 | Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment | 0 Participants |
p-value: 1Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact