Safety and Efficacy of Tenofovir Alafenamide for Chronic Hepatitis B Patients With Decompensated Liver Disease
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Complete virological suppression
研究概览
简要总结
TAF is a new prodrug of tenofovir, specifically designed to achieve higher intracellular active drug concentration allowing for dosing of only 25 mg once daily and thus can potentially lower the already relatively low risk of renal toxicity and bone loss with TDF. However, such renal and bone complications with TDF may become more pronounced in decompensated CHB patients10. In the phase 3 trials11, 12, TAF had demonstrated a compatible antiviral effect (noninferior efficacy), and a higher rate of alanine aminotransferase (ALT) normalization to TDF. TAF also demonstrated an improved renal function and less bone loss compared to TDF. Therefore, TAF was approved as the first line therapy for CHB patients with compensated liver function. The lack of data regarding TAF therapy in decompensated CHB patients raised the concern of safety and efficacy of TAF in this group of patients. A small, single arm Phase 2 switch study (GS-US-320-4035; Study 4035; NCT03180619) which has enrolled 31 subjects with CPT scores ≥7, either at time of screening or by history, who were virally suppressed on TDF and/or other oral antiviral agents is currently underway with favorable safety and efficacy results through 48 weeks.[Lim YS, Lin CY, Heo J, et al. EASL 2020, poster SAT442.] While Gilead Study 4035 will continue through 96 weeks of treatment, additional data in this population are thus needed, particularly in CHB patients who have decompensated liver disease and are not being treated and are viremic. Herein, we conduct the present study and aim to investigate the safety and efficacy of TAF in CHB patients with hepatic decompensation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant female, age ≥20 years
- •Chronic HBV infection with positive hepatitis B surface antigen (HBsAg) for at least 6 months at screening.
- •Hepatic decompensation, defined as Child-Turcotte-Pugh (CTP) score ≥7, or the presence of portal hypertension related complications including ascites, hepatic encephalopathy (<grade 2) at screening.
- •HBV NUC treatment naïve or experienced (except prior TAF) for Arm A or currently under HBV NUC treatment (except TAF) with HBV DNA < 20 IU/mL within 6 months prior screening for Arm B.
- •Patients with either liver cirrhosis or non-cirrhosis (defined by histology, non-invasive assessments, or imaging/clinical based diagnosis).
- •Estimated creatinine clearance ≥30 ml/min (using the Cockcroft-Gault method) at 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 solid organ (including liver), or bone marrow transplant.
- •Severe or uncontrolled comorbidities determined by the Investigator.
- •Currently ≥grade 2 hepatic encephalopathy, currently or history (within 60 days) of variceal bleeding, hepatorenal syndrome, refractory ascites or spontaneous bacterial peritonitis; cytopenia of absolute neutrophil count < 750/mm3, or hemoglobin < 8 g/dL, or platelet <30000/mm3; or MELD score ≥30 at screening.
- •Malignancy history including hepatocellular carcinoma, except basal cell skin cancer without recurrence for more than 5 years.
- •Acute exacerbation of HBV, defined as an elevation of alanine aminotransferase (ALT) activity to more than 10 times the upper limit of normal and more than twice the baseline value.
- •On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 16). 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.
研究组 & 干预措施
Arm A - initial TAF treatment group
cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and HBV NUC treatment naïve or experienced (except prior TAF) will receive initial treatment (Arm A) with TAF 25 mg/day.
干预措施: Tenofovir Alafenamide Tablets (Drug)
Arm B - switch to TAF treatment group
cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and currently under HBV NUC treatment (except TAF) with HBV DNA < 20 IU/mL within 6 months prior screening will switch (Arm B) to TAF 25 mg/day
干预措施: Tenofovir Alafenamide Tablets (Drug)
结局指标
主要结局
Complete virological suppression
时间窗: week 48
Proportion of patients treated with TAF who achieve complete virological suppression (HBV DNA \< 20 IU/ml) at week 48 of TAF therapy in per-protocol (PP) population.
次要结局
- Rate of virological response(week 96, and 144)
- Rate of ALT normalization(week 48, 96, and 144)
- Changes of serum creatinine(week 48, 96, and 144)
- Changes of calculated creatinine clearance(week 48, 96, and 144)
- Changes in blood glucose(week 48, 96, and 144)
- Rate of recovery from hepatic decompensation(week 48, 96, and 144)
- Liver transplant-free survival(week 48, 96, and 144)
- Changes in bone mineral density(week 144)
- Rate of adverse events(week 48)
- Rate of HBeAg loss/seroconversion, HBsAg loss/seroconversion(week 48, 96, and 144)
- Changes in value of transient elastography(week 144)
- Changes in body mass index(week 48, 96, and 144)
- Changes in blood lipid profile(week 48, 96, and 144)