A Phase 3, Randomized, Double-Blind Study to Evaluate the Safetyand Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD versusTenofovir Disoproxil Fumarate (TDF) 300 mg QD for theTreatment of HBeAg-Negative, Chronic Hepatitis B
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 390
- 试验地点
- 10
- 主要终点
- The proportion of participants with hepatitis B virus (HBV) DNA less than 29 IU per mL
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA less than 29 IU/mL at Week 48 infection, .To compare the efficacy of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B in regard to the proportion of subjects with plasma HBV DNA levels below 29 IU/mL at Weeks 96 and 144. To compare the biochemical (ALT normalization) response of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B at Weeks 48, 96, and 144.To compare the serological response (loss of HBsAg with seroconversion to anti-HBs) of TAF 25 mg QD versus TDF 300 mg QD for the treatment of HBeAg-negative, chronic hepatitis B at Weeks 48, 96, and 144.The duration of double-blind treatment is 144 weeks (96 weeks under Amendments 1 and 2). At Week 144, all subjects remaining on blinded treatment will be switched to the open-label TAF 25 mg QD extension period for up to an additional 240 weeks (Week 144 throughWeek 384/ED). Subjects already assigned to open-label TAF 25 mg QD at Week 96 per Amendment 1 or 2 will continue on open-label TAF 25 mg QD through Week 384/ED. All subjects who complete the double-blind period of treatment are eligible for participation in the open-label TAF 25 mg QD extension period. Subjects who permanently discontinue study drug(either prematurely [ED] or at the end of study [Week 384]) for reasons other than HBsAg loss with confirmed seroconversion to anti-HBs, will be followed every 4 weeks for 24 weeks off treatment or until initiation of alternative, commercially available HBV therapy, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2 Adult males and non-pregnant, non-lactating females, 18 years of age and older 3 Documented evidence of chronic HBV CHB infection 4 Hepatitis e antigen HBeAg negative, chronic hepatitis B with all of the following HBeAg-negative and hepatitis B e antibody HBeAb positive at screening Screening HBV DNA greater than or equal to 2 x 10 upon 4 IU per mL Screening serum alanine aminotransferase ALT level greater than 60 U/L males or greater than 38 U per L females and greater than 10 x the upper limit of the normal range ULN 5 Treatment-naive participants (defined as lower than 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue, OR treatment-experienced participants defined as participants meeting all entry criteria including HBV DNA and serum ALT criteria and with greater than or equal 12 weeks of previous treatment with any nucleoside or nucleotide analogue 6 Previous treatment with interferon pegylated or non pegylated must have ended at least 6 months prior to the baseline visit.
- •7 Adequate renal function 8 Normal ECG.
排除标准
- •1 Females who are breastfeeding 2 Males and females of reproductive potential who are unwilling to use an effective, protocol specified methods of contraception during the study 3 Co-infection with hepatitis C, HIV, or hepatitis D 4 Evidence of hepatocellular carcinoma 5 Any clinical and/or laboratory evidence of hepatic decompensation 6 Abnormal hematological and biochemical parameters, including aspartate aminotransferase AST greater than 10 x ULN 7 Received solid organ or bone marrow transplant 8 History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection participants under evaluation for possible malignancy are not eligible 9 Currently receiving therapy with immunomodulators eg corticosteroids investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion 10 Subjects receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or subjects with a known hypersensitivity to study drugs, metabolites, or formulation excipients 11 Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance 12 Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.
结局指标
主要结局
The proportion of participants with hepatitis B virus (HBV) DNA less than 29 IU per mL
时间窗: Week 48 | Week 96 | Week 144 | Week 240 | Week 384
The primary efficacy endpoint is determined by the achievement of HBV DNA less than 29 IU per mL at Week 48.
时间窗: Week 48 | Week 96 | Week 144 | Week 240 | Week 384
The proportion of subjects with plasma HBV DNA 29 IU/mL at
时间窗: Week 48 | Week 96 | Week 144 | Week 240 | Week 384
Weeks 96, 144, 240, and 384
时间窗: Week 48 | Week 96 | Week 144 | Week 240 | Week 384
The proportion of subjects with plasma HBV DNA 29 IU/mL(target not detected) at Weeks 48, 96, 144, 240, and 384
时间窗: Week 48 | Week 96 | Week 144 | Week 240 | Week 384
次要结局
- •Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48(•Change from baseline in serum creatinine at Week 48.)