COVID-19, SARS-CoV-2
Conditions
Keywords
SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19), Self-amplifying mRNA (samRNA), Human Immunodeficiency Virus (HIV)
Brief summary
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.
Detailed description
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.
Interventions
DRUGGRT-R912, samRNA-Spikebeta-TCE11
IM injection of GRT-R912. Doses will be decided after safety review of Part A.
DRUGGRT-R914, samRNA-Spikebeta-TCE9
Part A: 3 microgram (mcg), 10 mcg, or 30 mcg intramuscular (IM) injection of GRT-R914. Part C: IM injection of GRT-R914. Doses decided after safety review of Part A.
DRUGGRT-R918, samRNA-SpikeOmicron-N-TCE11
IM injection of GRT-R918. Doses will be decided after safety review of Part A.
Sponsors
Gritstone bio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* Current active infection with COVID-19. * 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-2. * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms | Up to 7 days after vaccination |
| Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms | Up to 7 days after vaccination |
| Number of Participants with Unsolicited Adverse Events | Up to 7 days after vaccination |
| Number of Participants with One or More Serious Adverse Events | Up to ~14 months after vaccination |
Secondary
| Measure | Time frame |
|---|---|
| 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 Antibody Binding and Neutralization Titers in Serum Samples | 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 |
| 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 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 |
| Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS | Up to ~14 months after vaccination |
Countries
South Africa
Outcome results
None listed