A Phase 1 SARS-CoV-2 Vaccine Study to Assess the Safety and Tolerability of GRT-R912, GRT-R914, and GRT-R918 Administered as Prime and/or Boost in Healthy Adult Participants and People Living With HIV
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 342
- 试验地点
- 4
- 主要终点
- Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms
研究概览
简要总结
The primary objective is to assess the safety and tolerability of samRNA vaccines GRT-R912, GRT-R914, and GRT-R918 when administered as prime and/or boost in healthy adult participants naïve to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV-2 convalescent, previously vaccinated, or non-vaccinated participants, and people living with HIV (PLWH) or HIV-negative.
详细描述
This Phase 1 clinical trial (CORAL-CEPI) will assess the potential of second-generation Coronavirus Disease 2019 (COVID-19) vaccines. These vaccines use a codon optimized Spike (S) cassette with additional T cell epitopes (TCE) (cassette S-TCE) covering multiple epitopes from non-spike proteins to safely drive strong, broad, and durable B cell and T cell immune responses to SARS-CoV-2. This trial will assess the potential to generate B cell and T cell responses against SARS-CoV-2 in both people living with HIV (PLWH) and HIV-negative participants, in participants who have previously been infected by SARS-CoV-2, and those who are naive to SARS-CoV-2, meaning they have neither been infected with nor vaccinated against SARS-CoV-2. GRT-R912, GRT-R914, and GRT-R918 are vaccines using a samRNA vector based and administered as either a single dose or two dose regimen, providing an option for a potent, single-modality approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or non-pregnant female at least 18 years and no more than 65 years of age at enrollment (Parts A, B, and C only).
- •No previous SARS-CoV-2 infection or recovered.
- •HIV-negative status confirmed by laboratory testing.
- •Additional inclusion criteria for PLWH:
- •Serum positive HIV test or history of HIV infection.
- •On anti-retroviral therapy for at least 3 months before screening and clinically stable.
- •Additional inclusion criteria for Part D (GRT-R918):
- •Male or non-pregnant female between 18 and <60 years of age at enrollment.
- •Male or non-pregnant female greater than or equal to 60 years of age at enrollment.
- •Received any authorized SARS-CoV-2 vaccine series at least 2 months prior to study vaccine.
排除标准
- •Current active infection with COVID-
- •Positive for SARS-CoV-2 by nasal swab polymerase chain reaction (PCR) at screening.
- •Currently receiving treatment or prevention agents with activity against SARS-CoV-
- •Breastfeeding, pregnant, or planning to become pregnant during the course of the study.
- •Received or plans to receive any non-study provided SARS-CoV-2 vaccine (including boost) during the study period (except for Part D).
- •Received or plans to receive any live, attenuated vaccine within 28 days before or after study vaccination.
- •Received or plans to receive any subunit or killed vaccine within 14 days before or after vaccination.
- •Received or plans to receive immunoglobulins and/or any blood products within the 3 months preceding the planned administration of first study vaccination or at any time during the study.
- •Currently active viral infection of hepatitis B virus or hepatitis C virus.
- •Additional exclusion criteria for PLWH:
- •Screening CD4+ T cell count ≤200 cells/mcL.
- •Viral load ≥10,000 virus particles/mL.
- •History of opportunistic illness indicative of Stage 3 HIV infection.
- •Acute febrile illness within 4 weeks before the first vaccination.
- •Additional exclusion criterion for Part D (GRT-R918) Cohorts D3, D4, D7, and D8:
- •Received last dose of any authorized SARS-CoV-2 vaccine series within 2 months prior to study vaccine.
研究组 & 干预措施
GRT-R914, HIV-negative (Part A)
Participants in this ≥18 to 65-year-old Part A are naïve to SARS-CoV-2 (Cohorts A1, A2, and A3) or SARS-CoV-2 convalescent (Cohorts A4, A5, A6). Cohorts will receive doses of GRT-R914 administered as prime and boost on Days 1 and Day 29, or as boost 6 months after primary SARS-CoV-2 infection.
干预措施: GRT-R914, samRNA-Spikebeta-TCE9 (Drug)
GRT-R912, HIV-negative (Part B)
Participants in this ≥18 to 65-year-old Part B are naïve to SARS-CoV-2 (Cohorts B1, B2) or SARS-CoV-2 convalescent (Cohorts B3, B4). Cohorts will receive doses of GRT-R912 administered as prime and boost on Days 1 and 29, or as boost 6 months after primary SARS-CoV-2 infection. Parts B, C, and D will be run in parallel.
干预措施: GRT-R912, samRNA-Spikebeta-TCE11 (Drug)
GRT-R912 or GRT-R914, People Living with HIV (PLWH) (Part C)
Participants in this ≥18 to 65-year-old Part C are people living with HIV but naïve to SARS-CoV-2 (Cohorts C1, C4) or living with HIV but SARS-CoV-2 convalescent (Cohorts C2, C3, C5, C6). Cohorts will receive doses of GRT-R912 or GRT-R914 administered as prime and boost on Days 1 and 29, or as boost 6 months after primary SARS-CoV-2 infection. Parts B, C, and D will be run in parallel.
干预措施: GRT-R912, samRNA-Spikebeta-TCE11 (Drug)
GRT-R912 or GRT-R914, People Living with HIV (PLWH) (Part C)
Participants in this ≥18 to 65-year-old Part C are people living with HIV but naïve to SARS-CoV-2 (Cohorts C1, C4) or living with HIV but SARS-CoV-2 convalescent (Cohorts C2, C3, C5, C6). Cohorts will receive doses of GRT-R912 or GRT-R914 administered as prime and boost on Days 1 and 29, or as boost 6 months after primary SARS-CoV-2 infection. Parts B, C, and D will be run in parallel.
干预措施: GRT-R914, samRNA-Spikebeta-TCE9 (Drug)
GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)
Participants will be ≥18 and <60 years or ≥60 years, HIV-Negative and PLWH with no prior vaccination to SARS-CoV-2 (Cohorts D1, D2, D5, D6) or with prior vaccination to SARS-CoV-2 (Cohorts D3, D4, D7, D8). Cohorts will receive doses of GRT-R918 administered as prime and boost on Days 1 and 29, or as boost ≥2 months after prior SARS-CoV-2 vaccination. Parts B, C, and D will be run in parallel.
干预措施: GRT-R918, samRNA-SpikeOmicron-N-TCE11 (Drug)
结局指标
主要结局
Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms
时间窗: Up to 7 days after vaccination
Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms
时间窗: Up to 7 days after vaccination
Number of Participants with Unsolicited Adverse Events
时间窗: Up to 7 days after vaccination
Number of Participants with One or More Serious Adverse Events
时间窗: Up to ~14 months after vaccination
次要结局
- Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples(Up to ~14 months after vaccination)
- Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples(Up to ~14 months after vaccination)
- Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS)(Up to ~14 months after vaccination)
- Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS(Up to ~14 months after vaccination)
- Response Rate of SARS-CoV-2- Specific CD4+ and CD8+ T cells by Interferon-Gamma Enzyme-linked Immunospot (ELISpot)(Up to ~14 months after vaccination)
- Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot(Up to ~14 months after vaccination)
- Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS(Up to ~14 months after vaccination)