Efficacy and Safety of Switching to Tenofovir Alafenamide for Chronic Hepatitis B Patients With Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(t)Ide Analogues
试验速览
- 阶段
- 4 期
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Rate of virological response
研究概览
简要总结
A total of 80 adult chronic hepatitis B patients with advanced liver fibrosis (including fibrosis stage 3 and cirrhosis), who are currently on nucleot(s)ide analogs (except tenofovir alafenamide) therapy with detectable HBV DNA after 52 weeks of therapy will switch prior NUCs to TAF 25 mg/day for 96 weeks
详细描述
Study Overview
Dosage regimen: Patients of CHB with advanced fibrosis and partial virological response to NUCs will be considered eligible for the present study. The enrollment will be up to the physician's discretion. The drug will be administered 1 pill (25 mg) per day orally, per manufacturers' instructions, and can be taken with food.
Compliance: Enrolled patients must be monitored according to the protocol, GCP, and clinical practice guidelines.
Study population: Approximately 80 adult CHB patients with advanced fibrosis (including fibrosis stage 3 and cirrhosis), who are currently on NUCs (except TAF) therapy with detectable HBV DNA after 52 weeks of therapy will switch prior NUCs to TAF 25 mg/day for 96 weeks. For patients of fibrosis stage 3, the numbers of enrolled patients will be no more than 40% of total enrolled patients.
Study Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age ≥20 years
- •CHB diagnosis confirmed by positive HBsAg or HBV DNA for more than 6 months, or documented history of CHB in medical record before initiation of NUC therapy.
- •Currently maintained on nucleot(s)ide analogues (except TAF) therapy for more than one year, with detectable HBV DNA after 52 weeks of therapy, detectable HBV DNA within 3-6 months prior to screening, and remains detectable HBV DNA at screening.
- •Patients with liver fibrosis stage 3 (defined as Metavir fibrosis stage 3 by liver biopsy, or fibrosis-4 score 3.25 ~ 6.49, or ARFI 1.80 ~ 1.99 m/s, or Fibroscan 9.5~12.4 kPa), or cirrhosis (defined as Metavir fibrosis stage 4 by liver biopsy, or APRI >2, or fibrosis-4 score ≥ 6.5, or ARFI ≥ 2.0 m/s, or Fibroscan ≥12.5 kPa, or image diagnosis with splenomegaly or esophageal/gastric varices) at the initiation of prior NUC therapy or during the prior NUC therapy. The liver biopsy should be within 5 years, or during the prior NUC therapy and other non-invasive assessments should be within 6 months at the initiation of NUC therapy or during the prior NUC therapy.
- •Estimated creatinine clearance > 15 ml/min (using the Cockcroft-Gault method) within 6 months prior to screening. (Note: multiply estimated rate by 0.85 for women).
- •Willing and able to provide informed consent
- •Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments
排除标准
- •Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
- •Previous recipient of a liver transplant
- •Co-infection with human immunodeficiency virus (HIV) or hepatitis C (HCV) or hepatitis D (HDV)
- •Severe or uncontrolled comorbidities, determined by the Investigator.
- •Known history of serum albumin level <3 g/dL, or total bilirubin level >3 mg/dL, or presence of ascites.
- •Known history of hepatic encephalopathy, and/or variceal bleeding.
- •Malignancy history including hepatocellular carcinoma, except cancers curable by surgical resection (e.g. basal cell skin cancer and squamous cell cancer within 5 yrs of screening).
- •On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 11). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening.
- •Males and females of reproductive potential who are unwilling to use "effective" protocol-specified method(s) of contraception during the study.
- •Current substance or alcohol abuse judged by the investigator to potentially interfere with subject compliance.
- •Any other clinical conditions that, in the opinion of the Investigator, would make the subject unsuitable or unable to comply with any of the study procedures
研究组 & 干预措施
Switch to TAF
Subjects who meet the inclusion and exclusion criteria will switch prior NUCs to TAF 25 mg/day for 96 weeks
干预措施: Tenofovir Alafenamide (Drug)
结局指标
主要结局
Rate of virological response
时间窗: at 48 weeks of TAF therapy.
HBV DNA \<LLOQ
次要结局
- Rate of ALT normalization(at week 48 and 96)
- Rate of virological response(at 96 weeks of treatment)
- Changes of serum creatinine(at week 48 and 96)
- Changes in liver fibrosis(at week 48 and 96)
- Changes of calculated creatinine clearance (Cockcroft-Gault)(at week 48 and 96)
- Changes in bone mineral density(at week 48 and 96)