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

Chronic Hepatitis B Clinical Trial

Official title:

Randomized Double-Blind Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B Virologically Suppressed for at Least Twelve Months on Tenofovir Disoproxil Fumarate, Tenofovir Alafenamide or Entecavir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03905655
• Other study ID #: RM08-2001
• Status: Completed
• Phase: Phase 2
• Start date: October 22, 2019
• Est. completion date: October 11, 2021

Study information

• Verified date: November 2023
• Source: Romark Laboratories L.C.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: October 11, 2021
• Est. primary completion date: March 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Romark Laboratories L.C.

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)	Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline	Baseline to 12 weeks
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	Baseline to 24 weeks after the end of treatment
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	8 weeks
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	12 weeks
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	12 weeks
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	12 weeks
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.	12 weeks
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).	Baseline to end of treatment