A Prospective Study to Investigate the Relationship Between Hepatitis B Surface Antigen (HBsAg) Loss and the Dynamics in Host and Viral Markers After Discontinuation of Nucleos(t)Ide Analog (NA) Treatment in Chronic Hepatitis B E-antigen Negative Patients With Low On-treatment HBsAg Level
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment
研究概览
简要总结
The purpose of this study is to assess the incidence of participants who reach hepatitis B surface antigen (HBsAg) seroclearance after discontinuing nucleos(t)ide analog (NA) therapy in participants with HBsAg less than or equal to (<=) 100 international units per milliliter (IU/mL) and participants with HBsAg greater than (>) 100 IU/mL to <= 500 IU/mL at baseline.
详细描述
Hepatitis B virus (HBV) virus infects the human liver. It consists of a nucleocapsid with hepatitis B core (HBc) protein and a membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic hepatitis B (CHB) virus infection may lead to liver cirrhosis and hepatocellular carcinoma (HCC). Recent guidelines (European Association for the Study of the Liver [EASL] guidelines, Asian Pacific Association for the Study of the Liver [APASL] guidelines) suggest that discontinuation of treatment with nucleos(t)ide analog (NA) (Entecavir [ETV], tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) in non-cirrhotic Hepatitis B e antigen (HBeAg) negative patients after a minimum of three years of viral suppression can trigger changes in virological and immune composition resulting in achieving HBsAg seroclearance (up to 25 percent [%]). The study will be conducted in 3 phases: screening phase (up to 6 weeks), baseline visit (1 day), and post-NA discontinuation phase (up to 96 weeks) which refers to the phase after baseline, in which treatment will be discontinued (off treatment). Discontinuation of NA treatment is considered as study intervention in this study. Collection of core liver biopsy, fine needle aspiration (FNA), and blood samples are considered study investigations/procedures. The participants will be followed for up to 2 years post-NA treatment discontinuation. The total duration of an individual participation will be up to 102 weeks (including up to 6 weeks for screening and baseline).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Medically stable on the basis of physical examination, medical history, vital signs, and clinical laboratory tests performed at screening and during the pre-biopsy assessments. If the results of the serum chemistry panel including liver enzymes, blood coagulation, other specific tests, or hematology are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study (in consultation with sponsor)
- •Hepatitis B surface antigen (HBsAg) less than or equal to (<=) 500 International units per milliliters (IU/mL) (and greater than [>] 5 IU/mL) at screening
- •Hepatitis B e antigen (HBeAg) less than (<) lower limit of quantification and hepatitis B e antibody (HBeAb) positive at screening
- •Normal liver ultrasound (at screening or within 3 months before screening [documented evidence])
- •Participants must have a body mass index between 18.0 and 35.0 Kilograms per meter square (kg/m^2), extremes included
排除标准
- •History of or signs of cirrhosis or portal hypertension (absence of nodules, no smooth liver contour, no normal portal vein, spleen size greater than or equal to [>=] 12 centimeters [cm]) or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 3 months prior to screening (based on documented evidence, if available) or at the time of screening. In case of suspicious findings on conventional ultrasound the participant may still be eligible if HCC or clinically relevant renal abnormalities have been ruled out by a more specific imaging procedure (contrast enhanced ultrasound, computed tomography [CT] or magnetic resonance imaging [MRI])
- •Participant's refusal to accept blood transfusions
- •Participants with clinically relevant drug or alcohol abuse within 12 months before screening
- •Received an investigational intervention or used an invasive investigational medical device within 3 months before the planned enrollment or is currently enrolled in an investigational study
- •Participants of Asian descent
结局指标
主要结局
Percentage of Participants with HBsAg Seroclearance After Discontinuation of NA Treatment
时间窗: At Week 96
Percentage of participants with HBsAg seroclearance after discontinuation of NA treatment will be reported.
Percentage of Participants with Hepatitis B Surface Antigen (HBsAg) Seroclearance After Discontinuation of Nucleos(t)ide Analog (NA) Treatment
时间窗: At Week 24
Percentage of participants with HBsAg seroclearance after discontinuation of NA treatment will be reported.
次要结局
- Change from Baseline Over Time in HBsAg Level(Baseline up to 96 weeks)
- Percentage of Participants with Abnormalities in Clinical Laboratory Parameters(Up to 96 weeks)
- Time to Achieve First HBsAg Seroclearance(Up to 96 weeks)
- Percentage of Participants with HBsAg Seroconversion(At Week 24, Week 48, and Week 96)
- Percentage of Sustained Clinical Responders(At Week 24, Week 48, and Week 96)
- Percentage of Participants with Flares(At Week 24, Week 48, and Week 96)
- Change from Baseline Over Time in HBV DNA level(Baseline up to 96 weeks)
- Percentage of Participants with Serious Adverse Events (SAEs)(Up to 96 weeks)
- Percentage of Participants Who Meet the NA Re-Treatment Criteria(Up to 96 weeks)