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

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-28
• Study Completion Date: 2024-03-06

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.

Conditions

COVID-19; SARS-CoV-2

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GRT-R914, samRNA-Spikebeta-TCE9

Intervention Type: 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, 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.

Group Type: EXPERIMENTAL

GRT-R912, samRNA-Spikebeta-TCE11

Intervention Type: 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)

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.

Group Type: EXPERIMENTAL

GRT-R912, samRNA-Spikebeta-TCE11

Intervention Type: DRUG

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

GRT-R914, samRNA-Spikebeta-TCE9

Intervention Type: 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, 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.

Group Type: EXPERIMENTAL

GRT-R918, samRNA-SpikeOmicron-N-TCE11

Intervention Type: DRUG

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

Interventions

GRT-R912, samRNA-Spikebeta-TCE11

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

Intervention Type: 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.

Intervention Type: DRUG

GRT-R918, samRNA-SpikeOmicron-N-TCE11

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

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gritstone bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Martin, DO

Role: STUDY_DIRECTOR

Gritstone bio, Inc.

Locations

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

Countries

South Africa

Other Identifiers

GO-012

Identifier Type: -

Identifier Source: org_study_id