A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Switching From Tenofovir Disoproxil Fumarate (TDF) 300 mg QD to Tenofovir Alafenamide (TAF) 25 mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 490
- 主要终点
- Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
研究概览
简要总结
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching to tenofovir alafenamide (TAF) versus continuing tenofovir disoproxil fumarate (TDF) in virologically suppressed adults with chronic hepatitis B virus (HBV) infection.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- •Adult male and non-pregnant, non-lactating females
- •Documented evidence of chronic hepatitis B virus (HBV) infection previously
- •Maintained on tenofovir disoproxil fumarate (TDF) 300 mg once daily for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA < lower limit of quantitation) for a minimum of 12 weeks prior to screening
- •Adequate renal function
- •Normal Electrocardiogram
排除标准
- •Pregnant women or women who are breastfeeding
- •Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study.
- •Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or human immunodeficiency virus (HIV)
- •Evidence of hepatocellular carcinoma
- •Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation
- •Abnormal hematological and biochemical parameters, including:
- •Hemoglobin < 10 g/dL
- •Absolute neutrophil count < 750/mm^3
- •Platelets ≤ 50,000/mm^3
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 × upper limit of the normal (ULN)
- •Albumin < 3.0 mg/ dL
- •International normalized ratio (INR) > 1.5 × ULN (unless stable on anticoagulant regimen)
- •Total bilirubin > 2.5 × ULN
- •Received solid organ or bone marrow transplant
- •Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Individuals under evaluation for possible malignancy are not eligible.
- •Currently receiving therapy with immunomodulators (eg, corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
- •Individuals receiving ongoing therapy with drugs not to be used with TAF or TDF or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients
- •Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
- •Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
- •Use of investigational agents within 3 months of screening, unless allowed by the sponsor
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
TAF 25 mg
Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks.
干预措施: TAF (Drug)
TAF 25 mg
Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks.
干预措施: TDF Placebo (Drug)
TDF 300 mg
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
干预措施: TAF (Drug)
TDF 300 mg
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
干预措施: TDF (Drug)
TDF 300 mg
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
干预措施: TAF Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
时间窗: Week 48
The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
次要结局
- Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48(Week 48)
- Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96(Week 96)
- Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96(Week 96)
- Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48(Week 48)
- Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm(Week 96)
- Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48(Weeks 48)
- Percentage of Participants With HBeAg Seroconversion at Week 48(Week 48)
- Percentage of Participants With HBeAg Loss at Week 96(Week 96)
- Percentage of Participants With HBeAg Seroconversion at Week 96(Week 96)
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48(Week 48)
- Percentage of Participants With HBsAg Seroconversion at Week 48(Week 48)
- Percentage of Participants With HBsAg Loss at Week 96(Week 96)
- Percentage of Participants With HBsAg Seroconversion at Week 96(Week 96)
- Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria)(Week 48)
- Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)(Week 48)
- Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)(Week 96)
- Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)(Week 96)
- Change From Baseline in FibroTest® Score at Week 48(Baseline; Week 48)
- Change From Baseline in FibroTest® Score at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Hip BMD at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Spine BMD at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Spine BMD at Week 96(Baseline; Week 96)
- Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48(Baseline; Week 48)
- Change From Baseline in eGFR-CG at Week 96(Baseline; Week 96)