A Phase 2 Study to Evaluate the Safety, Tolerability, and Efficacy of Regimens Containing VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 244
- 试验地点
- 1
- 主要终点
- Proportion of participants with treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a phase 2 study in which participants with chronic hepatitis B virus (HBV) infection will receive VIR-2218, VIR-3434 and/or PEG-IFNα and be assessed for safety, tolerability, and efficacy
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ages 18 - <66 years
- •Chronic HBV infection for >/= 6 months
- •On NRTI therapy for >/= 2 months at the time of screening
排除标准
- •Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
- •Significant fibrosis or cirrhosis
- •History or evidence of drug or alcohol abuse
- •History of chronic liver disease from any cause other than chronic HBV infection
- •History of hepatic decompensation
- •History of anaphylaxis
- •History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434
- •History of immune complex disease
- •History of known contraindication to any interferon product
研究组 & 干预措施
Cohort 1a (VIR-2218 + VIR-3434)
Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
干预措施: VIR-2218 (Drug)
Cohort 1a (VIR-2218 + VIR-3434)
Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
干预措施: VIR-3434 (Drug)
Cohort 2a (VIR-2218 + VIR-3434)
Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
干预措施: VIR-2218 (Drug)
Cohort 2a (VIR-2218 + VIR-3434)
Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
干预措施: VIR-3434 (Drug)
Cohort 3a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
干预措施: VIR-2218 (Drug)
Cohort 3a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
干预措施: VIR-3434 (Drug)
Cohort 4a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
干预措施: VIR-2218 (Drug)
Cohort 4a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
干预措施: VIR-3434 (Drug)
Cohort 5a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
干预措施: VIR-2218 (Drug)
Cohort 5a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
干预措施: VIR-3434 (Drug)
Cohort 6a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
干预措施: VIR-2218 (Drug)
Cohort 6a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
干预措施: VIR-3434 (Drug)
Cohort 7a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks
干预措施: VIR-2218 (Drug)
Cohort 7a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks
干预措施: VIR-3434 (Drug)
Cohort 8a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks
干预措施: VIR-2218 (Drug)
Cohort 8a (VIR-2218 + VIR-3434)
Participants will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks
干预措施: VIR-3434 (Drug)
Cohort 1b (VIR-3434)
Participants will receive multiple doses of VIR-3434 for 44 weeks
干预措施: VIR-3434 (Drug)
Cohort 2b (VIR-3434)
Participants will receive multiple doses of VIR-3434 for 20 weeks
干预措施: VIR-3434 (Drug)
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
干预措施: VIR-2218 (Drug)
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
干预措施: VIR-3434 (Drug)
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
干预措施: PEG-IFNα (Drug)
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
干预措施: VIR-2218 (Drug)
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
干预措施: VIR-3434 (Drug)
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
干预措施: PEG-IFNα (Drug)
Cohort 1d (VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-3434 + PEG-IFNα for 48 weeks
干预措施: VIR-3434 (Drug)
Cohort 1d (VIR-3434 + PEG-IFNα)
Participants will receive multiple doses of VIR-3434 + PEG-IFNα for 48 weeks
干预措施: PEG-IFNα (Drug)
结局指标
主要结局
Proportion of participants with treatment-emergent adverse events (TEAEs)
时间窗: Up to 72 weeks
Proportion of participants with serious adverse events (SAEs)
时间窗: Up to 72 weeks
Proportion of participants with hepatitis B surface antigen (HBsAg) loss (defined as undetectable HBsAg) at end of treatment
时间窗: Up to 48 weeks
Proportion of participants with HBsAg loss (defined as undetectable HBsAg) at 24 weeks post-end of treatment
时间窗: Up to 72 weeks
次要结局
- Nadir and maximum reduction of serum HBsAg from baseline(Up to 110 weeks)
- Absolute serum HBsAg and change from baseline across all timepoints in the study(Up to 110 weeks)
- Proportion of participants achieving sustained suppression of HBV DNA (< lower limit of quantification (LLOQ) for >= 24 weeks after discontinuation of all treatment, including NRTIs)(Up to 110 weeks)
- For hepatitis B e-antigen (HBeAg)-positive participants: Proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion at any timepoint(Up to 110 weeks)
- For HBeAg-positive participants: Time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion(Up to 110 weeks)
- Cmax(Up to 110 weeks)
- AUClast(Up to 110 weeks)
- t1/2(Up to 110 weeks)
- CL/F(Up to 110 weeks)
- Number of participants with incidence and titers of anti-drug antibody (ADA) (if applicable) to VIR-3434(Up to 110 weeks)
- Proportion of participants meeting criteria for nucleotide reverse transcriptase inhibitors (NRTI) discontinuation(Up to 60 weeks)
- Proportion of participants meeting criteria for NRTI retreatment(Up to 110 weeks)
- Proportion of participants achieving undetectable HBsAg and sustained suppression of HBV DNA [below the LLOQ, target not detected (TND)] >/= 24 weeks after discontinuation of all treatment, including NRTIs(Up to 110 weeks)
- Proportion of participants with serum HBsAg < 10 IU/mL at end of treatment(Up to 48 weeks)
- Proportion of participants with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment(Up to 72 weeks)
- Proportion of participants with anti-HBs seroconversion(Up to 110 weeks)
- Time to achieve nadir of serum HBsAg(Up to 110 weeks)
- Time to achieve serum HBsAg loss(Up to 110 weeks)