Clinical trial NCT05435027: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
SARS-CoV-2
Keywords: SARS-CoV-2 vaccine
Coronavirus Disease (COVID-19)
Self-amplifying mRNA (samRNA)
Human Immunodeficiency Virus (HIV)
Lead sponsor: Gritstone bio, Inc.
Sponsor class: INDUSTRY
First posted: 2022-06-28
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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.

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.

Primary outcomes:
measure: Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms
timeFrame: Up to 7 days after vaccination
measure: Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms
timeFrame: Up to 7 days after vaccination
measure: Number of Participants with Unsolicited Adverse Events
timeFrame: Up to 7 days after vaccination
measure: Number of Participants with One or More Serious Adverse Events
timeFrame: Up to ~14 months after vaccination
Secondary outcomes:
measure: Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
timeFrame: Up to ~14 months after vaccination
measure: Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
timeFrame: Up to ~14 months after vaccination
measure: Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS)
timeFrame: Up to ~14 months after vaccination
measure: Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS
timeFrame: Up to ~14 months after vaccination
measure: Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS
timeFrame: Up to ~14 months after vaccination
measure: Response Rate of SARS-CoV-2- Specific CD4+ and CD8+ T cells by Interferon-Gamma Enzyme-linked Immunospot (ELISpot)
timeFrame: Up to ~14 months after vaccination
measure: Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot
timeFrame: Up to ~14 months after vaccination
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research Centre
city: Johannesburg
country: South Africa
facility: WITS RHI Shandukani Research Centre
city: Johannesburg
country: South Africa
facility: Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit
city: Pretoria
country: South Africa
facility: Setshaba Research Center
Study officials:
affiliation: Gritstone bio, Inc.
name: Elizabeth Martin, DO
role: STUDY_DIRECTOR
References: