Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Drug: GRT-R912, samRNA-Spikebeta-TCE11
* Drug: GRT-R914, samRNA-Spikebeta-TCE9
* Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11


Participation Criteria
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Eligibility Criteria
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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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRT-R914, HIV-negative (Part A)<br>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/or boost on Days 1 and Day 29, or as boost 6 months after primary SARS-CoV-2 infection. | Drug: GRT-R914, samRNA-Spikebeta-TCE9<br>* 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.<br>|
| Experimental: GRT-R912, HIV-negative (Part B)<br>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/or 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. | Drug: GRT-R912, samRNA-Spikebeta-TCE11<br>* IM injection of GRT-R912. Doses will be decided after safety review of Part A.<br>|
| Experimental: GRT-R912, People Living with HIV (PLWH) (Part C)<br>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. | Drug: GRT-R912, samRNA-Spikebeta-TCE11<br>* IM injection of GRT-R912. Doses will be decided after safety review of Part A.<br>Drug: GRT-R914, samRNA-Spikebeta-TCE9<br>* 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.<br>|
| Experimental: GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)<br>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. | Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11<br>* IM injection of GRT-R918. Doses will be decided after safety review of Part A.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19), Self-amplifying mRNA (samRNA), Human Immunodeficiency Virus (HIV)