A Platform Study Evaluating the Efficacy and Safety of Investigational Therapies in Participants With Chronic Hepatitis B Infection (PREVAIL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 14
- 主要终点
- STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment
研究概览
简要总结
This is a Phase 1b/2 platform study framework to evaluate the safety and efficacy of investigational candidate(s) and their combinations as potential treatments for adults with chronic hepatitis B virus infection.
详细描述
VIR-SHB1-V201 (STRIVE) Sub-Protocol A is a Phase 2 study under the PREVAIL platform trial. This is a multi-center, open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434, VIR-2218, PEGASYS (PEG-IFNα), and nucleotide reverse transcriptase inhibitors (NRTI) in noncirrhotic adult participants with chronic HBV infection that have not received prior NRTI or PEGASYS treatment.
VIR-SHB1-V202 (THRIVE) Sub-Protocol B is a Phase 2 study under the PREVAIL platform trial. This is a multi-center open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434 and NRTI with or without VIR-2218 in noncirrhotic adult participants with low viral burden of chronic HBV infection.
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
- 18 Years 至 66 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ages 18 or older
- •Chronic HBV infection for >/= 6 months
- •Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on 2 occasions at least 6 months apart based on previous or current laboratory documentation
- •STRIVE: HBeAg positive or negative, HBV DNA > 2,000 IU/mL, ALT > ULN and ≤ 5x ULN
- •THRIVE: Must be/have the following, within the 1-year period prior to screening: HBeAg negative, HBV DNA ≤ 2,000 IU/mL, ALT ≤ ULN
排除标准
- •Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
- •History of clinically significant liver disease from non-HBV etiology
- •History or current evidence of hepatic decompensation
- •Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV).
- •History or clinical evidence of alcohol or drug abuse
- •STRIVE and THRIVE: Significant fibrosis or cirrhosis
- •STRIVE and THRIVE: History of immune complex disease
- •STRIVE and THRIVE: History of autoimmune disorder
- •STRIVE and THRIVE: History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434
- •STRIVE: Prior NRTI or PEG-IFN therapy
- •STRIVE: History of known contraindication to any interferon product
- •THRIVE: Prior NRTI therapy < 24 weeks of study or any prior PEG-IFN therapy
研究组 & 干预措施
STRIVE: Cohort 2a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
干预措施: TDF (Drug)
STRIVE: Cohort 3a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total
干预措施: VIR-3434 (Drug)
STRIVE: Cohort 3a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total
干预措施: TDF (Drug)
STRIVE: Cohort 1a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
干预措施: VIR-3434 (Drug)
STRIVE: Cohort 1a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
干预措施: TDF (Drug)
STRIVE: Cohort 2a (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total
干预措施: VIR-3434 (Drug)
STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total
干预措施: VIR-3434 (Drug)
STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total
干预措施: VIR-2218 (Drug)
STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total
干预措施: TDF (Drug)
STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα)
Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total
干预措施: VIR-3434 (Drug)
STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα)
Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total
干预措施: VIR-2218 (Drug)
STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα)
Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total
干预措施: TDF (Drug)
STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα)
Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total
干预措施: PEG-IFNα (Drug)
THRIVE: Cohort 1b (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks
干预措施: VIR-3434 (Drug)
THRIVE: Cohort 1b (VIR-3434 + TDF)
Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks
干预措施: TDF (Drug)
THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total
干预措施: VIR-3434 (Drug)
THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total
干预措施: VIR-2218 (Drug)
THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF)
Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total
干预措施: TDF (Drug)
结局指标
主要结局
STRIVE and THRIVE: Proportion of Participants Achieving Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) at the End of Treatment
时间窗: Up to 48 weeks
次要结局
- STRIVE and THRIVE: Proportion of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to 96 weeks)
- STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at End of Treatment(Up to 48 weeks)
- STRIVE and THRIVE: Proportion of Participants With Serum HBsAg ≤ 10 IU/mL at 24 Weeks Post-end of Treatment(Up to 72 weeks)
- STRIVE and THRIVE: Serum HBsAg Levels and Change From Baseline Across Timepoints in the Study(Up to 96 weeks)
- STRIVE and THRIVE: Serum HBsAg Level at Nadir During the Study(Up to 96 weeks)
- STRIVE and THRIVE: Time to Achieve Nadir of Serum HBsAg During the Study(Up to 96 weeks)
- STRIVE and THRIVE: Time to Achieve Serum HBsAg Loss (< 0.05 IU/mL)(Up to 96 weeks)
- STRIVE and THRIVE: Proportion of Participants With HBsAg Loss With Anti-HBs Seroconversion at End of Treatment and at 24 Weeks Post-end of Treatment(Up to 76 weeks)
- STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit(Up to 96 weeks)
- STRIVE: Proportion of Participants With HBsAg Loss (<0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment(Up to 72 weeks)
- STRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at the F48 Follow-Up Visit(Up to 96 weeks)
- STRIVE: For HBeAg-positive Participants: Proportion of Participants With HBeAg Loss (Undetectable HBeAg) and/or Anti-HBe Seroconversion(Up to 72 weeks)
- STRIVE: Incidence and Titers of Anti-drug Antibodies (ADA; if Applicable) to VIR-3434(Up to 96 weeks)
- STRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study(Up to 96 weeks)
- STRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ) Across Timepoints in the Study(Up to 96 weeks)
- STRIVE: Proportion of Participants Achieving ALT ≤ ULN Across Timepoints in the Study(Up to 96 weeks)
- THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) With HBsAg Loss (< 0.05 IU/mL) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks(Up to 92 weeks)
- THRIVE: Proportion of Participants Achieving HBsAg Loss (< 0.05 IU/mL) at End of Treatment and at 24 Weeks Post-end of Treatment(Up to 44 weeks)
- THRIVE: Proportion of Participants Achieving Sustained Suppression of HBV DNA (< LLOQ) After Discontinuation of All Treatment at 24 Weeks and at 48 Weeks(Up to 68 weeks)
- THRIVE: Incidence and Titers of ADA (if Applicable) to VIR-3434(Up to 92 weeks)
- THRIVE: Mean Change in Serum HBsAg Level From Baseline Across Timepoints in the Study(Up to 92 weeks)
- THRIVE: Proportion of Participants Achieving HBV DNA (< LLOQ)(Up to 92 weeks)