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

Sponsor

Romark Laboratories L.C. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03905655

Collaborator

(none)

Enrollment

Location

Arms

37.3

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Placebo Oral Tablet Drug: Nitazoxanide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients are randomized 1:1:1:1 (12 subjects per group)Patients are randomized 1:1:1:1 (12 subjects per group)

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 22, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group 1 Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy	Drug: Placebo Oral Tablet Number of placebo tablets administered orally depends on the arm
Active Comparator: 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	Drug: Placebo Oral Tablet Number of placebo tablets administered orally depends on the arm Drug: Nitazoxanide Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm Other Names: NTZ, NT-300
Active Comparator: 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	Drug: Placebo Oral Tablet Number of placebo tablets administered orally depends on the arm Drug: Nitazoxanide Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm Other Names: NTZ, NT-300
Active Comparator: Group 4 Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy	Drug: Nitazoxanide Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm Other Names: NTZ, NT-300

Outcome Measures

Primary Outcome Measures

Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) [Baseline to 12 weeks]
Mean change in qHBsAg

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age at least 21 years
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))
Hepatitis B e Antigen (HBeAg) negative
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
Quantitative HBsAg greater than 100 IU/mL
Alanine Aminotransferase (ALT) below 1.5 times the upper limit of normal
Able to comply with the study requirements

Exclusion Criteria:

Unable to take oral medications
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.
Any investigational drug therapy within 30 days prior to enrollment
Other causes of liver disease
Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) based on an enzyme immunoassay (EIA)
History of alcoholism or with an alcohol consumption of greater than 40 g per day
Clinically unstable
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
History of hypersensitivity or intolerance to NTZ or any of the excipients comprising the NTZ tablets
Hepatocellular carcinoma
Decompensated liver disease including history of ascites, bleeding esophageal varices, portal hypertension or hepatic encephalopathy
FibroScan® score greater than 11 or history of cirrhosis on liver biopsy
Creatinine clearance <65 ml/minute (by the Cockcroft-Gault equation using ideal body weight)
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
Malignant disease within 3 years of trial entry
Rheumatological conditions, inflammatory bowel disease or psoriasis requiring or anticipated to require biological/immunosuppressive therapies
Subjects taking or anticipated to need medications considered to be major CYP2C8 substrates