Back to resultsStudy of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)
Primary Purpose
COVID-19, SARS-CoV-2
Status
Active
Phase
Phase 1
Locations
South Africa
Study Type
Interventional
Intervention
GRT-R912, samRNA-Spikebeta-TCE11
GRT-R914, samRNA-Spikebeta-TCE9
GRT-R918, samRNA-SpikeOmicron-N-TCE11
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19 focused on measuring SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19), Self-amplifying mRNA (samRNA), Human Immunodeficiency Virus (HIV)
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.
Sites / Locations
- Newtown Clinical Research Centre
- WITS RHI Shandukani Research Centre
- Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit
- Setshaba Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
GRT-R914, HIV-negative (Part A)
GRT-R912, HIV-negative (Part B)
GRT-R912, People Living with HIV (PLWH) (Part C)
GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)
Arm Description
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/or boost on Days 1 and Day 29, or as boost 6 months after primary SARS-CoV-2 infection.
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/or 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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms
Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms
Number of Participants with Unsolicited Adverse Events
Number of Participants with One or More Serious Adverse Events
Secondary Outcome Measures
Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS)
Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS
Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS
Response Rate of SARS-CoV-2- Specific CD4+ and CD8+ T cells by Interferon-Gamma Enzyme-linked Immunospot (ELISpot)
Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05435027
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 28, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gritstone bio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV-2
Keywords
SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19), Self-amplifying mRNA (samRNA), Human Immunodeficiency Virus (HIV)
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
342 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GRT-R914, HIV-negative (Part A)
Arm Type
Experimental
Arm Description
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/or boost on Days 1 and Day 29, or as boost 6 months after primary SARS-CoV-2 infection.
Arm Title
GRT-R912, HIV-negative (Part B)
Arm Type
Experimental
Arm Description
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/or 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.
Arm Title
GRT-R912, People Living with HIV (PLWH) (Part C)
Arm Type
Experimental
Arm Description
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.
Arm Title
GRT-R918, HIV-negative and PLWH, With and Without Prior Vaccination (Part D)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GRT-R912, samRNA-Spikebeta-TCE11
Intervention Description
IM injection of GRT-R912. Doses will be decided after safety review of Part A.
Intervention Type
Drug
Intervention Name(s)
GRT-R914, samRNA-Spikebeta-TCE9
Intervention Description
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
Intervention Name(s)
GRT-R918, samRNA-SpikeOmicron-N-TCE11
Intervention Description
IM injection of GRT-R918. Doses will be decided after safety review of Part A.
Primary Outcome Measure Information:
Title
Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms
Time Frame
Up to 7 days after vaccination
Title
Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms
Time Frame
Up to 7 days after vaccination
Title
Number of Participants with Unsolicited Adverse Events
Time Frame
Up to 7 days after vaccination
Title
Number of Participants with One or More Serious Adverse Events
Time Frame
Up to ~14 months after vaccination
Secondary Outcome Measure Information:
Title
Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
Time Frame
Up to ~14 months after vaccination
Title
Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples
Time Frame
Up to ~14 months after vaccination
Title
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
Title
Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS
Time Frame
Up to ~14 months after vaccination
Title
Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS
Time Frame
Up to ~14 months after vaccination
Title
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
Title
Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot
Time Frame
Up to ~14 months after vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedro Garbes, MD
Organizational Affiliation
Gritstone Bio
Official's Role
Study Director
Facility Information:
Facility Name
Newtown Clinical Research Centre
City
Johannesburg
Country
South Africa
Facility Name
WITS RHI Shandukani Research Centre
City
Johannesburg
Country
South Africa
Facility Name
Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit
City
Johannesburg
Country
South Africa
Facility Name
Setshaba Research Center
City
Pretoria
Country
South Africa
12. IPD Sharing Statement
Learn more about this trial
Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)
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