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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Placebo Oral Tablet (Drug)
Group 1
Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
干预措施: Placebo Oral Tablet (Drug)
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
干预措施: Placebo Oral Tablet (Drug)
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
干预措施: Nitazoxanide (Drug)
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
干预措施: Nitazoxanide (Drug)
Group 4
Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy
干预措施: Nitazoxanide (Drug)
结局指标
主要结局
Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
时间窗: Baseline to 12 weeks
Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline
次要结局
- Hepatitis B Surface Antigen (HBsAg) Loss(12 weeks)
- Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment(8 weeks)
- 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)
- Hepatitis B Surface Antigen (HBsAg) Seroconversion(12 weeks)
- Hepatitis B Virus DNA Suppression(12 weeks)
- Change in Fibrosis-4 (FIB-4) Score(12 weeks)
- Change in FibroScan Score(Baseline to end of treatment)