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

Phase 2

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Placebo Oral Tablet; Drug: Nitazoxanide

• Registration Number: NCT03905655
• Lead Sponsor: Romark Laboratories L.C.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-04
• Study First Submitted QC: 2019-04-04
• Study First Posted: 2019-04-05
• Study Start: 2019-10-22
• Primary Completion: 2021-03-10
• Study Completion: 2021-10-11
• Results First Submitted: 2023-10-06
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-03
• Last Update Submitted: 2023-11-03
• Results First Posted: 2023-11-07
• Last Update Posted: 2023-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Placebo Oral Tablet	Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Group 2	Placebo Oral Tablet	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
Group 3	Placebo Oral Tablet	Two 300 mg NTZ tablets and one placebo tablet administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Group 4	Nitazoxanide	Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
Group 2	Nitazoxanide	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
Group 3	Nitazoxanide	Two 300 mg NTZ tablets and one placebo tablet administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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
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
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).

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore