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

NCT ID: NCT03905655

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-22
• Study Completion Date: 2021-10-11

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).

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Number of placebo tablets administered orally depends on the arm

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

Group Type: ACTIVE_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Number of placebo tablets administered orally depends on the arm

Nitazoxanide

Intervention Type: DRUG

Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm

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

Group Type: ACTIVE_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Number of placebo tablets administered orally depends on the arm

Nitazoxanide

Intervention Type: DRUG

Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm

Group 4

Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy

Group Type: ACTIVE_COMPARATOR

Nitazoxanide

Intervention Type: DRUG

Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm

Interventions

Placebo Oral Tablet

Number of placebo tablets administered orally depends on the arm

Intervention Type: DRUG

Nitazoxanide

Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm

Intervention Type: DRUG

Other Intervention Names

NTZ, NT-300

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Romark Laboratories L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RM08-2001

Identifier Type: -

Identifier Source: org_study_id