A Phase 1a/1b Study to Evaluate the Safety and Tolerability of Repeated Doses of Nonreplicating Arenavirus Vector Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B (CHB)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 9
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The goal of this clinical study is to learn more about GS-2829 and GS-6779 in healthy participants and participants with CHB.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Phase 1a and 1b:
- •Body mass index (BMI) of ≤ 32.0 kg/m^
- •Non-diabetic without impaired glucose tolerance.
- •No evidence of cardiac disease based on 12 lead electrocardiogram (ECG).
- •Phase 1a (Healthy Individuals) only:
- •Aged 18 through 60 years.
- •No prior history of Hepatitis B infection with a negative hepatitis B surface antigen (HBsAg) and Hepatitis B (HBV) core antibody.
- •Phase 1b (Virally Suppressed chronic hepatitis B (CHB) Individuals)):
- •Aged 18 through 65 years.
- •Documented CHB and HBsAg ≤ 5000 IU/mL at screening.
- •No evidence of advanced fibrosis by Fibroscan (defined as Fibroscan < 9 kilo pascal (kPa) within 6 months of screening).
- •Diagnosed with CHB on suppressive oral antiviral for ≥ 6 months.
- •Must have received an approved HBV-active oral antiviral agent for ≥ 6 months prior to screening with HBV DNA below lower limit of quantification (LLOQ) for ≥ 3 months prior to screening and with no plan to stop HBV-active antivirals during the study.
排除标准
- •Phase 1a and 1b:
- •Use of any systemic antibiotics within 30 days of screening.
- •Receipt of any HBV vaccine within 12 months of screening visit or planning HBV vaccination during the study period.
- •Receipt of any investigational product within 3 months or vaccine within 3 months of screening (with the exception of influenza and severe acute respiratory syndrome (SARs) coronavirus (COV) - 2 (SARS-CoV-2) vaccines, which if needed, should be administered at least 14 days before or after an investigational product administration).
- •Receipt of immunoglobulin or other blood products within 3 months of screening.
- •Positive serum pregnancy test at screening or positive urine pregnancy on Day
- •Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, other immune or cytokine-based therapies).
- •Participation in any other clinical study (including observational studies) without prior approval from the sponsor is prohibited while participating in the study.
- •Note - Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a : Cohort 4 (Healthy Participants) : GS-2829 and GS-6779 High Dose (2 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: GS-6779 (Biological)
Phase 1a : Cohort 1 (Healthy Participants) : GS-2829 Low Dose (2 injections)
Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 focus-forming unit (FFU)/mL) or placebo as intramuscular (IM) injection on Days 1 and 57.
干预措施: GS-2829 (Biological)
Phase 1a : Cohort 1 (Healthy Participants) : GS-2829 Low Dose (2 injections)
Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 focus-forming unit (FFU)/mL) or placebo as intramuscular (IM) injection on Days 1 and 57.
干预措施: Placebo (Biological)
Phase 1a : Cohort 2 (Healthy Participants) : GS-6779 Low Dose (2 injections)
Healthy participants will receive a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57.
干预措施: GS-6779 (Biological)
Phase 1a : Cohort 2 (Healthy Participants) : GS-6779 Low Dose (2 injections)
Healthy participants will receive a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57.
干预措施: Placebo (Biological)
Phase 1a : Cohort 3 (Healthy Participants) : GS-2829 and GS-6779 Low Dose (2 cycles)
Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: GS-2829 (Biological)
Phase 1a : Cohort 3 (Healthy Participants) : GS-2829 and GS-6779 Low Dose (2 cycles)
Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: GS-6779 (Biological)
Phase 1a : Cohort 3 (Healthy Participants) : GS-2829 and GS-6779 Low Dose (2 cycles)
Healthy participants will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: Placebo (Biological)
Phase 1a : Cohort 4 (Healthy Participants) : GS-2829 and GS-6779 High Dose (2 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: GS-2829 (Biological)
Phase 1a : Cohort 4 (Healthy Participants) : GS-2829 and GS-6779 High Dose (2 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection, on Days 29 and 85.
干预措施: Placebo (Biological)
Phase 1a : Cohort 8 (Healthy Participants) : GS-2829 and GS-6779 High Dose (3 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: GS-2829 (Biological)
Phase 1a : Cohort 8 (Healthy Participants) : GS-2829 and GS-6779 High Dose (3 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: GS-6779 (Biological)
Phase 1a : Cohort 8 (Healthy Participants) : GS-2829 and GS-6779 High Dose (3 cycles)
Healthy participants will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: Placebo (Biological)
Phase 1b : Cohort 5 (VS Participants with CHB) : GS-2829 and GS-6779 Low Dose (2 cycles)
Virally suppressed (VS) participants with Chronic Hepatitis B (CHB) will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: GS-2829 (Biological)
Phase 1b : Cohort 5 (VS Participants with CHB) : GS-2829 and GS-6779 Low Dose (2 cycles)
Virally suppressed (VS) participants with Chronic Hepatitis B (CHB) will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: GS-6779 (Biological)
Phase 1b : Cohort 5 (VS Participants with CHB) : GS-2829 and GS-6779 Low Dose (2 cycles)
Virally suppressed (VS) participants with Chronic Hepatitis B (CHB) will receive a single low dose of GS-2829 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single low dose of GS-6779 (≥ 0.5 x 10^6 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: Placebo (Biological)
Phase 1b : Cohort 6 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (2 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: GS-2829 (Biological)
Phase 1b : Cohort 6 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (2 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: GS-6779 (Biological)
Phase 1b : Cohort 6 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (2 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1 and 57; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29 and 85.
干预措施: Placebo (Biological)
Phase 1b : Cohort 7 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (3 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: GS-2829 (Biological)
Phase 1b : Cohort 7 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (3 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: GS-6779 (Biological)
Phase 1b : Cohort 7 (VS Participants with CHB) : GS-2829 and GS-6779 High Dose (3 cycles)
VS participants with CHB will receive a single high dose of GS-2829 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 1, 57 and 113; and a single high dose of GS-6779 (≥ 0.5 x 10^7 FFU/mL) or placebo as IM injection on Days 29, 85 and 141.
干预措施: Placebo (Biological)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: First dose date to end of study (followed up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2], Day 253 [cohorts 3, 4, 5, 6], and Day 309 [cohorts 7 and 8])
Treatment-emergent adverse events (TEAEs) were defined as any AE with a start date on or after the study drug start date; or any AE that led to premature discontinuation of study drug. An SAE is defined as an event that, at any dose, results in the following: Death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
时间窗: First dose date to end of study (followed up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2], Day 253 [cohorts 3, 4, 5, 6], and Day 309 [cohorts 7 and 8])
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any time postbaseline. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed postbaseline will be considered treatment emergent.
次要结局
- Percentage of Participants With ≥ 3-Fold Increase in Vaccine-Induced Hepatitis B Virus (HBV) Specific T-Cell Responses(Up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2]) or up to 12 weeks post last dose (up to Day 169 [cohorts 3, 4, 5, 6]; Day 225 [cohorts 7 and 8]))
- Mean Peak Levels of Vaccine-Induced HBV Specific T-Cell Responses(Up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2]) or up to 12 weeks post last dose (up to Day 169 [cohorts 3, 4, 5, 6]; Day 225 [cohorts 7 and 8]))