---
title: Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)
nct_id: NCT05435027
overall_status: COMPLETED
phase: PHASE1
sponsor: Gritstone bio, Inc.
study_type: INTERVENTIONAL
primary_condition: COVID-19
countries: South Africa
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT05435027.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05435027"
ct_last_update_post_date: 2024-03-12
last_seen_at: "2026-05-12T07:02:47.885Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)

**Official Title:** 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

**NCT ID:** [NCT05435027](https://clinicaltrials.gov/study/NCT05435027)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE1
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 342
- **Lead Sponsor:** Gritstone bio, Inc.
- **Conditions:** COVID-19, SARS-CoV-2
- **Start Date:** 2022-02-28
- **Completion Date:** 2024-03-06
- **CT.gov Last Update:** 2024-03-12

## 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.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **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 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.
```

## Arms

- **GRT-R914, HIV-negative (Part A)** (EXPERIMENTAL) — 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.
- **GRT-R912, HIV-negative (Part B)** (EXPERIMENTAL) — 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.
- **GRT-R912 or GRT-R914, People Living with HIV (PLWH) (Part C)** (EXPERIMENTAL) — 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.
- **GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)** (EXPERIMENTAL) — 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.

## Interventions

- **GRT-R912, samRNA-Spikebeta-TCE11** (DRUG) — IM injection of GRT-R912. Doses will be decided after safety review of Part A.
- **GRT-R914, samRNA-Spikebeta-TCE9** (DRUG) — 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.
- **GRT-R918, samRNA-SpikeOmicron-N-TCE11** (DRUG) — IM injection of GRT-R918. Doses will be decided after safety review of Part A.

## Primary Outcomes

- **Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms** _(time frame: Up to 7 days after vaccination)_
- **Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms** _(time frame: Up to 7 days after vaccination)_
- **Number of Participants with Unsolicited Adverse Events** _(time frame: Up to 7 days after vaccination)_
- **Number of Participants with One or More Serious Adverse Events** _(time frame: Up to ~14 months after vaccination)_

## Secondary Outcomes

- **Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples** _(time frame: Up to ~14 months after vaccination)_
- **Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples** _(time frame: Up to ~14 months after vaccination)_
- **Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS)** _(time frame: Up to ~14 months after vaccination)_
- **Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS** _(time frame: Up to ~14 months after vaccination)_
- **Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS** _(time frame: 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)** _(time frame: Up to ~14 months after vaccination)_
- **Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot** _(time frame: Up to ~14 months after vaccination)_

## Locations (4)

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

## Recent Field Changes (last 30 days)

- `design.phases` — added _(2026-05-12)_
- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.newtown clinical research centre|johannesburg||south africa` — added _(2026-05-12)_
- `locations.wits rhi shandukani research centre|johannesburg||south africa` — added _(2026-05-12)_
- `locations.wits vaccines & infections diseases analytics (vida) research unit|johannesburg||south africa` — added _(2026-05-12)_
- `locations.setshaba research center|pretoria||south africa` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT05435027.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT05435027*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*