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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: GRT-R914, samRNA-Spikebeta-TCE9; Drug: GRT-R912, samRNA-Spikebeta-TCE11; Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11

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.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Johannesburg, South Africa
    • Newtown Clinical Research Centre
  • Johannesburg, South Africa
    • Wits RHI Shandukani Research Centre
  • Johannesburg, South Africa
    • Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit
  • Pretoria, South Africa
    • Setshaba Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11; IM injection of GRT-R918. Doses will be decided after safety review of Part A.
Experimental: 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.	Drug: GRT-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.
Experimental: 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.	Drug: GRT-R912, samRNA-Spikebeta-TCE11; IM injection of GRT-R912. Doses will be decided after safety review of Part A.
Experimental: 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.	Drug: GRT-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.; Drug: GRT-R912, samRNA-Spikebeta-TCE11; IM injection of GRT-R912. Doses will be decided after safety review of Part A.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Gritstone bio, Inc.
• Investigators: Study Director: Elizabeth Martin, DO, Gritstone bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): March 6, 2024
• Study Completion (Actual): March 6, 2024

Study Registration Dates

• First Submitted: June 24, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Human Immunodeficiency Virus (HIV); SARS-CoV-2 vaccine; Coronavirus Disease (COVID-19); Self-amplifying mRNA (samRNA)
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; COVID-19; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: GO-012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No