A Phase 4, Randomized, Open-label, Active-Controlled, Superiority Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon α-2a (Pegasys®) Versus Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon α-2a Monotherapy for 48 Weeks in Non-Cirrhotic Subjects With HBeAg-Positive or HBeAg-Negative Chronic Hepatitis B (CHB)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 751
- 试验地点
- 170
- 主要终点
- Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen (HBsAg).
The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups. Following an initial 48 weeks of treatment, participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and those meeting TDF retreatment and flare management criteria will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen (HBsAg) or HBV DNA for at least 6 months) prior to baseline
- •Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose ≥ 24 weeks prior to screening are also eligible.
- •Positive or negative for hepatitis B e antigen (HBeAg)
- •HBV DNA ≥ 20,000 IU/ml (HBeAg-positive participants) and ≥ 2,000 IU/ml (HBeAg-negative participants)
- •Alanine aminotransferase (ALT) > 54 U/L and ≤ 400 U/L for men and > 36 U/L and ≤ 300 U/L for women
- •Creatinine clearance ≥ 70 mL/min
- •Negative serum pregnancy test for females of childbearing potential
- •Sexually active females of childbearing potential must agree to use a protocol-recommended method of contraception throughout the study and for 30 days following the last dose of study medication
- •Lactating females must agree to discontinue nursing before initiation of study investigational medicinal product
排除标准
- •Known bridging fibrosis or cirrhosis and/or decompensated liver disease
- •Evidence of hepatocellular carcinoma
- •Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures)
- •Absolute neutrophil count < 1,500/mm^3, platelet < 100,000/mm^3, hemoglobin < 10 g/dL (female) or < 11 g/dL (male)
- •History of severe depression or severe psychiatric disease
- •Thyroid dysfunction
- •Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
研究组 & 干预措施
TDF+Peg-IFN 48 Weeks
TDF plus Peg-IFN for 48 weeks
干预措施: TDF (Drug)
TDF+Peg-IFN 48 Weeks
TDF plus Peg-IFN for 48 weeks
干预措施: Peg-IFN (Drug)
TDF 48 Weeks + Peg-IFN 16 Weeks
TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks
干预措施: TDF (Drug)
TDF 48 Weeks + Peg-IFN 16 Weeks
TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks
干预措施: Peg-IFN (Drug)
TDF 120 Weeks
TDF monotherapy for 120 weeks
干预措施: TDF (Drug)
Peg-IFN 48 Weeks
Peg-IFN monotherapy for 48 weeks
干预措施: Peg-IFN (Drug)
结局指标
主要结局
Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
时间窗: Baseline; Week 72
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. Proportions are based on a Kaplan-Meier estimate. The analysis visit window for Week 72 comprised Week 70 through Week 78, so results up to Week 78 are included in this analysis.
次要结局
- Percentage of Participants With HBsAg Loss at Weeks 96 and 120(Baseline; Weeks 96 and 120)
- Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120(Baseline; Weeks 72, 96, and 120)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 72(Baseline; Week 72)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 96(Baseline; Week 96)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 120(Baseline; Week 120)
- Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72(Week 72)
- Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96(Week 96)
- Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120(Week 120)
- Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With TDF (48 Weeks) Plus Peg-IFN (16 Weeks) Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone(Baseline; Week 72)
- Percentage of Participants With Normal ALT at Week 72(Week 72)
- Percentage of Participants With Normal ALT at Week 96(Week 96)
- Percentage of Participants With Normal ALT at Week 120(Week 120)
- Percentage of Participants Who Required Retreatment(Up to 120 weeks)