跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT03753074
NCT03753074进行中（未招募）4 期

A Multinational, Multicenter, Open-label, Randomized Controlled Trial to Investigate the Effectiveness of Tenofovir Alafenamide in Reducing Clinical Events in Chronic Hepatitis B Patients Beyond Treatment Indications by Current Guidelines

Young-Suk Lim10 个研究点 分布在 1 个国家目标入组 780 人开始时间: 2019年2月18日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
进行中（未招募）
发起方
入组人数
780
试验地点
10
主要终点
the occurrence of composite events during follow-up observation
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL < 8) is expected to bring improvement in long-term clinical outcomes. This expected result may expand the treatment indications in patients with CHB based on age and HBV-DNA in contrast to current international guidelines of CHB.

详细描述

Study objectives: To investigate whether TAF treatment reduce clinical events (HCC, death, liver decompensation, portal hypertensive complications, and liver transplantation) in CHB patients beyond treatment indications by current guidelines

Study procedure: 780 subjects will be randomized in a 1:1 ratio (A:B) either to receive TAF 25 mg QD or to receive best supportive care after stratification according to the HBeAg status.

The study duration is 12 years. During treatment period, among treatment arm B, subjects who are indicated for antiviral treatment will be treated with TAF as follows:

  1. Based on the AASLD 2018 Guidelines of CHB (ALT 70≥ for male, 50≥ for female)
  2. 40≤ALT levels<70 IU/L (males) or 40≤ ALT levels<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
  3. If they were clinically judged to have cirrhosis by investigators and confirmed with Fibroscan (≥ 12.0 kPa).
  • Treatment Arm A: 390 subjects administered TAF 25 mg once daily
  • Treatment Arm B: 390 subjects received best supportive care

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
None

入排标准

年龄范围
40 Years 至 80 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Patients must meet all of the following criteria to be eligible to participate in the study
  • •Patient must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
  • •Male or female, 40 to 80 years of age
  • •Positive for HBsAg or HBV DNA for at least 6 months or more
  • •HBeAg positive or negative
  • •No evidence of liver cirrhosis (platelet count ≥100,000/mm3)
  • •serum HBV DNA ≥ 4 log10 IU/mL and ≤ 8 log10 IU/mL
  • •Serum ALT level <70 if male, <50 if female
  • •Estimated creatinine clearance ≥ 30 ml/min based on serum creatinine as measured at the screening evaluation
  • •Patient is willing and able to comply with all study requirements

排除标准

  • •Patients who meet any of the following exclusion criteria are not to be enrolled in this study
  • •Co-infection with HCV, HDV, HIV (Confirmed by nucleic acid tests)
  • •Abusing alcohol (more than 60 g/day) or illicit drugs
  • •Patients with history of hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
  • •4-1) Evidence of cirrhosis, including any of follows:
  • •Platelet count <100,000/mm3
  • •Esophagogastric varices on endoscopy
  • •Evidence of clinically significant portal hypertension
  • •Fibroscan ≥ 12.0 kPa (If the test was done in 3 months before the time of screening.) and confirmed to have liver cirrhosis by an investigator
  • •4-2) 40≤ALT levels<70 IU/L (males) or 40≤ ALT levels<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
  • •Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
  • •Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agents
  • •Received solid organ or bone marrow transplant
  • •Known hypersensitivity to study drugs, metabolites, or formulation excipients
  • •Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study or unable to comply with dosing requirements
  • •Use of investigational agents within 6 months of screening, unless allowed by the Sponsor or Investigator
  • •Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
  • •Any malignant tumor in the preceding five years. However, a history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years
  • •Pregnant or breastfeeding or willing to be pregnant
  • •Participating in other clinical trials to administer medication. However, it is possible to participate if it is not an antiviral agent or immunosuppressant related clinical trial.

研究组 & 干预措施

Treatment Arm A (TAF)

Experimental

390 subjects administered Tenofovir Alafenamide 25 mg once daily

干预措施: Tenofovir Alafenamide (Drug)

结局指标

主要结局

the occurrence of composite events during follow-up observation

时间窗: At year 4

the occurrence of composite events during follow-up observation(including death, liver transplantation, or decompensated liver diseases \[Child-Pugh score≥7\], complications of portal hypertension \[ascites, gastroesophageal varices\] or HCC

次要结局

  • Cumulative incidence rate of liver transplantation among HBeAg-positive or HBeAg-negative(At year 4, 8 and 12)
  • Cumulative incidence rate of liver decompensation among HBeAg-positive or HBeAg-negative(At year 4, 8 and 12)
  • Cumulative incidence rate of portal hypertensive complications(At year 4, 8 and 12)
  • Rate of receiving nucleos(t)ide analogue by meeting reimbursement criteria of treatment among Treatment ARM B subjects(At year 4, 8 and 12)
  • Change of fibroscan(At year 4, 8 and 12)
  • Cumulative incidence rate of HCC among HBeAg-positive or HBeAg-negative Patients(At year 4, 8 and 12)
  • All cause-mortality among HBeAg-positive or HBeAg-negative(At year 4, 8 and 12)
  • Cumulative incidence rate of portal hypertensive complications among HBeAg-positive or HBeAg-negative(At year 4, 8 and 12)
  • Cumulative rate of patients with clinical events(At year 4, 8 and 12)
  • Change of FIB-4(At year 4, 8 and 12)
  • Cumulative incidence rate of liver transplantation among subjects according to baseline ALT level (normal ALT and elevated ALT)(At year 4, 8 and 12)
  • Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 6 months of enrollment(At year 4, 8 and 12)
  • Cumulative incidence rate of liver decompensation(At year 4, 8 and 12)
  • Rate of HBeAg seroclearance and seroconversion(At year 4, 8 and 12)
  • Change of APRI index(At year 4, 8 and 12)
  • All cause-mortality among subjects according to baseline ALT level (normal ALT and elevated ALT)(At year 4, 8 and 12)
  • Cumulative incidence rate of portal hypertensive complications among subjects according to baseline ALT level (normal ALT and elevated ALT)(At year 4, 8 and 12)
  • Cumulative incidence rate of HCC(At year 4, 8 and 12)
  • All-cause mortality(At year 4, 8 and 12)
  • Cumulative incidence rate of liver transplantation(At year 4, 8 and 12)
  • Virologic response defined as HBV DNA less than 15 IU/mL(At year 4, 8 and 12)
  • Rate of ALT normalization(At year 4, 8 and 12)
  • Cumulative incidence rate of HCC among subjects according to baseline ALT level (normal ALT and elevated ALT)(At year 4, 8 and 12)
  • Cumulative incidence rate of liver decompensation among subjects according to baseline ALT level (normal ALT and elevated ALT)(At year 4, 8 and 12)
  • Cumulative and annual rate of patients with clinical events (death, liver transplantation, liver decompensation, portal hypertensive complications, and HCC) after excluding patients who occurrs clinical events within 12 months of enrollment(At year 4, 8 and 12)
  • Cumulative and annual rate of patients with clinical events in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical(At year 4, 8 and 12)
  • Cumulative and annual rate of patients with clinical events in patients with normal ALT (<40 U/L) at the time of enrollment, after excluding patients who occurrs clinical events within 12 months of enrollment(At year 4, 8 and 12)

研究者

发起方
Young-Suk Lim
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Young-Suk Lim

Professor

Asan Medical Center

研究点 (10)

Loading locations...

相似试验

Unknown
不适用
Maternal Therapy With TAF Versus TDF to Prevent Vertical Transmission of Hepatitis BHepatitis B, ChronicPregnancy Related
NCT04211805New Discovery LLC450
Unknown
3 期
A RCT of TNF and ENT in the Treatment of Long-term Prognosis With Hepatitis B-related HCC After Curative ResectionHepatocellular Carcinoma Recurrent
NCT04392700Sun Yat-sen University706
招募中
不适用
Tenofovir Alafenamide Switch Therapy in Chronic Hepatitis BPatient SatisfactionDrug AdherenceEfficacy, SelfSafety Issues
NCT05583006Taichung Veterans General Hospital60
Unknown
不适用
The Efficacy and Safety of TAF vs Other NAs in Patients With LVLChronic Hepatitis bCirrhosis Due to Hepatitis B
NCT04501224Third Affiliated Hospital, Sun Yat-Sen University200
招募中
不适用
TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load.Non-cirrhotic, Chronic Hepatitis B
NCT05195450Institute of Liver and Biliary Sciences, India200
Effectiveness of TAF in Reducing Clinical Events in... | 临床试验