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

• Sponsor: Gritstone bio, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05435027
• Collaborator: (none)
• Enrollment: 340
• Locations: 3
• Arms: 4
• Anticipated Duration (Months): 21.1
• Patients Per Site: 113.3
• Patients Per Site Per Month: 5.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; SARS-CoV-2	Drug: GRT-R912, samRNA-Spikebeta-TCE11; Drug: GRT-R914, samRNA-Spikebeta-TCE9; Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11	Phase 1

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 340 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Feb 28, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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/or boost on Days 1 and Day 29, or as boost 6 months after primary SARS-CoV-2 infection.	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.
Experimental: 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/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.	Drug: GRT-R912, samRNA-Spikebeta-TCE11; IM injection of GRT-R912. Doses will be decided after safety review of Part A.
Experimental: GRT-R912, 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.	Drug: GRT-R912, samRNA-Spikebeta-TCE11; IM injection of GRT-R912. Doses will be decided after safety review of Part A.; 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.
Experimental: 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.	Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11; IM injection of GRT-R918. Doses will be decided after safety review of Part A.

Outcome Measures

Primary Outcome Measures

1. Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms [Up to 7 days after vaccination]

2. Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms [Up to 7 days after vaccination]

3. Number of Participants with Unsolicited Adverse Events [Up to 7 days after vaccination]

4. Number of Participants with One or More Serious Adverse Events [Up to ~14 months after vaccination]

Secondary Outcome Measures

1. Response Rate of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples [Up to ~14 months after vaccination]

2. Magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples [Up to ~14 months after vaccination]

3. Response Rate of SARS-CoV-2 Specific CD4+ and CD8+ T cells by Intracellular Cytokine Staining (ICS) [Up to ~14 months after vaccination]

4. Magnitude of SARS-CoV-2 Specific CD4+ and CD8+ T cell Response by ICS [Up to ~14 months after vaccination]

5. Functional Profiling of SARS-CoV-2 Specific CD4+ and CD8+ T cells by ICS [Up to ~14 months after vaccination]

6. 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]

7. Magnitude of SARS-CoV-2- Specific CD4+ and CD8+ T cell Response by Interferon-Gamma ELISpot [Up to ~14 months after vaccination]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	WITS RHI Shandukani Research Centre	Johannesburg		South Africa
2	Wits Vaccines & Infections Diseases Analytics (VIDA) Research Unit	Johannesburg		South Africa
3	Setshaba Research Center	Pretoria		South Africa

Sponsors and Collaborators

• Gritstone bio, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gritstone bio, Inc.
• ClinicalTrials.gov Identifier: NCT05435027
• Other Study ID Numbers: GO-012
• First Posted: Jun 28, 2022
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gritstone bio, Inc.: SARS-CoV-2 vaccine; Coronavirus Disease (COVID-19); Self-amplifying mRNA (samRNA); Human Immunodeficiency Virus (HIV)
• Additional relevant MeSH terms: COVID-19; Acquired Immunodeficiency Syndrome; HIV Infections

Study Results

No Results Posted as of Aug 19, 2022