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

NCT05435027 | Completed Phase 1

• 1 other identifier: GO-012
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 4

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.

Conditions

COVID-19; SARS-CoV-2

Keywords

SARS-CoV-2 vaccine; Coronavirus Disease (COVID-19); Self-amplifying mRNA (samRNA); Human Immunodeficiency Virus (HIV)

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• 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

Study Arms (4)

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.

Drug: GRT-R914, samRNA-Spikebeta-TCE9

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.

Drug: GRT-R912, samRNA-Spikebeta-TCE11

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.

Drug: GRT-R912, samRNA-Spikebeta-TCE11; Drug: GRT-R914, samRNA-Spikebeta-TCE9

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.

Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11

Interventions

GRT-R912, samRNA-Spikebeta-TCE11 DRUG

IM injection of GRT-R912. Doses will be decided after safety review of Part A.

GRT-R912 or GRT-R914, People Living with HIV (PLWH) (Part C); GRT-R912, HIV-negative (Part B)

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-R912 or GRT-R914, People Living with HIV (PLWH) (Part C); GRT-R914, HIV-negative (Part A)

GRT-R918, samRNA-SpikeOmicron-N-TCE11 DRUG

IM injection of GRT-R918. Doses will be decided after safety review of Part A.

GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Serum positive HIV test or history of HIV infection.
• On anti-retroviral therapy for at least 3 months before screening and clinically stable.
• 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.

You may not qualify if:

• 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.
• 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.
• \- Received last dose of any authorized SARS-CoV-2 vaccine series within 2 months prior to study vaccine.

Sponsors & Collaborators

• Gritstone bio, Inc.: lead

Study Sites (4)

Newtown Clinical Research Centre

Johannesburg, South Africa

Location

WITS RHI Shandukani Research Centre

Johannesburg, South Africa

Location

Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit

Johannesburg, South Africa

Location

Setshaba Research Center

Pretoria, South Africa

Location

MeSH Terms

Conditions

COVID-19; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Elizabeth Martin, DO

  Gritstone bio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: June 28, 2022
• Study Start: February 28, 2022
• Primary Completion: March 6, 2024
• Study Completion: March 6, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

ZA (4)