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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05435027
• Other study ID #: GO-012
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2022
• Est. completion date: March 6, 2024

Study information

• Verified date: March 2024
• Source: Gritstone bio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: March 6, 2024
• Est. primary completion date: March 6, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• COVID-19
• HIV Infections
• SARS-CoV-2

Intervention

Drug:
• GRT-R912, samRNA-Spikebeta-TCE11
IM injection of GRT-R912. Doses will be decided after safety review of Part A.
• 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.
• GRT-R918, samRNA-SpikeOmicron-N-TCE11
IM injection of GRT-R918. Doses will be decided after safety review of Part A.

Locations

Country	Name	City	State
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	Johannesburg
South Africa	Setshaba Research Center	Pretoria

Sponsors (1)

Lead Sponsor	Collaborator
Gritstone bio, Inc.

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms		Up to 7 days after vaccination
Primary	Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms		Up to 7 days after vaccination
Primary	Number of Participants with Unsolicited Adverse Events		Up to 7 days after vaccination
Primary	Number of Participants with One or More Serious Adverse Events		Up to ~14 months after vaccination
Secondary	Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples		Up to ~14 months after vaccination
Secondary	Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples		Up to ~14 months after vaccination
Secondary	Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS)		Up to ~14 months after vaccination
Secondary	Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS		Up to ~14 months after vaccination
Secondary	Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS		Up to ~14 months after vaccination
Secondary	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
Secondary	Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot		Up to ~14 months after vaccination