Clinical trial NCT03905655: Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2019-04-05
Enrollment: 51
Sex: ALL
Minimum age (years): 21
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized 1:1:1:1 (12 subjects per group)
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment
timeFrame: Baseline to 24 weeks after the end of treatment
measure: Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment
timeFrame: 8 weeks
measure: Hepatitis B Surface Antigen (HBsAg) Loss
timeFrame: 12 weeks
measure: Hepatitis B Surface Antigen (HBsAg) Seroconversion
timeFrame: 12 weeks
measure: Hepatitis B Virus DNA Suppression
timeFrame: 12 weeks
measure: Change in Fibrosis-4 (FIB-4) Score
timeFrame: 12 weeks
measure: Change in FibroScan Score
timeFrame: Baseline to end of treatment
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
References: