Study of GRT-R910 COVID-19 Boost Vaccine in Healthy Volunteers

Gritstone bio, Inc.45 enrolled

Overview

The primary objective was to assess the safety and tolerability of 2 different doses (10 or 30 µg) of GRT-R910 when administered as a boost in healthy adults previously vaccinated with the AstraZeneca, Janssen/Johnson and Johnson, Moderna, or Pfizer/BioNTech Coronavirus disease 2019 (COVID-19) vaccines.

This trial studied a self-amplifying messenger ribonucleic acid (samRNA) based vaccine (GRT-R910) in previously vaccinated adults (≥18 years). GRT-R910 uses a codon optimized, prefusion stabilized Spike (S) cassette with additional T cell epitopes (TCEs) covering multiple epitopes from non-spike proteins to safely drive strong, broad, and durable B and T cell immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

COVID-19

Interventions

GRT-R910BIOLOGICAL

Injection administered intramuscularly

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * For Cohorts 1 and 2, have received AstraZeneca's AZD1222 COVID-19 prime and boost vaccine (Covishield®, Vaxzevria®), with the last dose received at least 2 months or more prior to Day 1. * For Cohort 3, have received a primary series of an adenoviral (AstraZeneca AZD1222 \[Covishield®, Vaxzevria®\] or Janssen \[Janssen COVID-19 Vaccine\]) COVID-19 vaccine (under emergency supply procedures or upon full approval and may have received booster doses of an authorized vaccine), with the last dose received at least 2 months or more prior to Day 1. * For Cohorts 4 and 6, have received a primary series of an mRNA (Pfizer/BioNTech \[Comirnaty®\] or Moderna \[Spikevax®\]) COVID-19 vaccine (under emergency supply procedures or upon full approval and may have received booster doses of an authorized vaccine), with the last dose received at least 2 months or more prior to Day 1. * Agree to refrain from blood donation during the course of the study. * Women of childbearing potential (WOCBP)\* must agree to avoid pregnancy and be willing to use a highly effective method of contraception\*\* consistently for 30 days prior to the first study vaccine and for at least 60 days after the last study vaccine * Male subjects of childbearing potential must agree to the use of condoms to ensure effective contraception with a female partner from the time of study vaccination until 3 months after vaccination. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after the last vaccination. Male subjects of childbearing potential are biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy. * Plan to remain living in the area for the duration of the study. Exclusion Criteria: * History of prior confirmed COVID-19 (cohorts 1 and 2). * History of prior confirmed (polymerase chain reaction \[PCR\] or antigen test positive) COVID-19 infection as confirmed by a diagnostic laboratory less than 16 weeks (112 days) prior to enrollment (Cohorts 3, 4, and 6). * Positive for SARS-CoV-2 (N-specific) antibody testing and had a history of upper respiratory illness consistent with COVID-19 within the 112 days prior to enrollment (Cohorts 3, 4, and 6). * Prior receipt of a SARS-CoV-2 vaccine other than AstraZeneca's AZD1222 (Covishield®, Vaxzevria®), JNJ-78436735, Pfizer/BioNTech (Comirnaty®), Moderna (Spikevax®), other approved or investigational adenovirus vectored vaccines, approved or investigational vaccines with a lipid nanoparticle (LNP) component, or any other approved or investigational vaccine likely to impact the interpretation of the trial data. * On current treatment or prevention agents with activity against SARS-CoV-2. * Participation in another research study involving receipt of an investigational product in the 60 days preceding enrollment or planned use during the study period. * Receipt or planned receipt of any live, attenuated vaccine within 28 days before or after study vaccination. * Receipt or planned receipt of any subunit or killed vaccine within 14 days before or after vaccination. * Administration of 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. * Breastfeeding, pregnant, or planning to become pregnant during the course of the study. * Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection with CD4+ T-cells \< 400/mm3, asplenia, recurrent, severe infections and chronic (more than 14 continuous days) immunosuppressant medication within the past 6 months (inhaled, ophthalmic, and topical steroids are allowed). * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain (or any immediate allergic reaction of any severity to polysorbate due to potential cross-reactive hypersensitivity with the PEG component of the vaccine). * Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema. * Any history of anaphylaxis, including but not limited to reaction to vaccination. * History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). * History of serious ongoing, unstable psychiatric condition that in the opinion of the investigator would interfere with study participation. * Bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture. * Suspected or known current alcohol abuse that in the opinion of the investigator would impede compliance with the protocol and schedules of assessments. * Suspected or known current alcohol abuse that in the opinion of the investigator would impede compliance with the protocol and schedules of assessments. Suspected or known drug abuse in the 5 years preceding enrollment. * Any other condition that in the opinion of the investigator would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results.

Locations (3)

University Hospitals Birmingham NHS

Birmingham, United Kingdom

University Hospital of Leicester NHS Trust

Leicester, United Kingdom

Manchester University

Manchester, United Kingdom

Outcomes

Primary Outcomes

Number of Participants With at Least One Solicited Local Adverse Event (AE) Within 8 Days After the Injection of Prime Dose

An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited local AEs included injection site pain, injection site tenderness, injection site erythema, injection site edema/induration. Solicited AEs (reactogenicity) were collected using a memory aid.

Time frame: Within 8 Days After the Injection of Prime Dose on Day 1

Number of Participants With at Least One Solicited Local AE Within 8 Days After the Injection of Booster Dose

Time frame: Within 8 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)

Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Prime Dose

An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited systemic AEs included headache, fatigue, malaise, myalgia, arthralgia, nausea, fever, and chills. Solicited AEs (reactogenicity) were collected using a memory aid.

Time frame: Within 8 Days After the Injection of Prime Dose on Day 1

Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Booster Dose

Data from ClinicalTrials.gov

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An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. Solicited systemic AEs included headache, fatigue, malaise, myalgia, arthralgia, nausea, fever, and chills. Solicited AEs (reactogenicity) were collected using a memory aid.

Time frame: Within 8 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)

Number of Participants With at Least One Unsolicited Treatment-emergent AEs (TEAEs) Within 28 Days After the Injection of Prime Dose

An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure.

Time frame: Within 28 Days After the Injection of Prime Dose on Day 1

Number of Participants With at Least One Unsolicited TEAEs Within 28 Days After the Injection of Booster Dose

An AE was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related in a participant or clinical investigation participant who administered a pharmaceutical product regardless of its causal relationship to the study treatment. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure.

Time frame: Within 28 Days After the Injection of Booster Dose on Day 113 (Cohorts 1, 2); Within 8 Days After the Injection of Booster Dose on Day 29 (Cohorts 3, 4, 6)

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 120

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 8

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 37 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 37

Change From Baseline in Hemoglobin at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Hemoglobin at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Hemoglobin at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 120

Change From Baseline in Hemoglobin at Day 8 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 8

Change From Baseline in Hemoglobin at Day 37 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 37

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 120

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 8

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 37 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 37

Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Bilirubin and Creatinine at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 120

Change From Baseline in Bilirubin and Creatinine at Day 8 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 8

Change From Baseline in Bilirubin and Creatinine at Day 37 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 37

Change From Baseline in Creatine Kinase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Creatine Kinase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 8

Change From Baseline in Creatine Kinase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)

Time frame: Baseline, Day 120

Change From Baseline in Creatine Kinase at Day 8 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 8

Change From Baseline in Creatine Kinase at Day 37 in Cohorts 3, 4, and 6

Time frame: Baseline, Day 37

Number of Participants With Treatment-emergent Serious AEs (SAEs), AE of Special Interest (AESIs) Including Potentially Immune-mediated Medical Conditions (PIMMCs), Medically Attended AEs (MAAEs), and New Onset Chronic Medical Conditions (NOCMCs)

An AE or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, with or without a causal relationship with the vaccine. A TEAE was defined as any event not observed before the first vaccination or any event observed before the first vaccination that worsens in intensity or frequency after exposure. A treatment-emergent SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. Adverse events of special interest were serologically or virologically confirmed SARS-CoV-2 infection or severe COVID-19, NOCMCs, MAAE (hospitalization, an emergency room visit or an otherwise unscheduled visit to or from medical personnel for any reason), and PIMMCs.

Time frame: Day 1 Up to 16 months

Secondary Outcomes

Change From Baseline in Immunoglobulin (Ig)G Level (Spike Wild Type [WT] Variant)

Sera were analyzed for Spike (WT variant)-specific IgG levels pre and post administration of GRT-R910 via enzyme-linked immunosorbent assay (ELISA) and reported as ELISA laboratory units (ELU)/mL (amount of antibodies in the sample according to the unit assigned by the standard).

Time frame: Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209, 293, 365, 394, 478

Change From Baseline in Neutralizing Antibody (nAb) Levels

Neutralizing antibody titers against live virus were assessed via microneutralization assay. Neutralizing antibody levels were measured for the following variants: WT, Alpha, Beta, Delta, Gamma.

Time frame: For WT: Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209 293, 365, 394, 478; For Alpha, Beta, Delta, Gamma:Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209 293, 365, 394

Number of Participants With Immunogenicity Response by Spike IgG and nAb Variants

Immunogenicity response defined as \>= 2-fold change in the levels from baseline. Response rate was assessed by Spike IgG wild type and nAb Variants \[wild type, alpha, beta, gamma, delta\]. Number of participants with immunogenicity response at any post-baseline timepoint are provided.

Time frame: Baseline to 478 days

Change From Baseline in T Cell Response by Spike Pools (ex Vivo ELISpot)

Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. T cell responses to SARS-CoV-2 D614G were assessed via ex vivo IFNγ ELISpot assay (methods). Cells were stimulated with overlapping peptide (OLP) pools containing peptides that were 15 amino acids in length (15mers) and spanning both S subunits (Spike pool 1-2, 3-4 \[S1\], 5-6, and 7-8 \[S2\]).

Time frame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478

Change From Baseline in T Cell Response by T Cell Epitope (TCE) Pools (ex Vivo ELISpot)

PBMCs were isolated from whole blood. T cell responses to conserved SARS-CoV-2 viral epitopes were assessed via ex vivo IFNγ ELISpot assay (methods). Responses to Nucleocapsid (Nuc) and open reading frame 3a (ORF3a)/Membrane TCE regions were assessed using OLP pools.

Time frame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478

Change From Baseline in Immunogenicity Response by TCE Pools (in Vitro Stimulation)

PBMCs were isolated from whole blood. T cell responses to conserved SARS-CoV-2 viral epitopes were assessed via IFNγ ELISpot assay following in vitro stimulation. Responses to Nuc, ORF3a, and membrane TCE regions were assessed using OLP pools.

Time frame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293

Number of Participants With Immunogenicity Response by Spike Pools and TCE Pools (ex Vivo ELISpot)

T cell responses to SARS-CoV-2 D614G and conserved non-Spike epitopes were assessed via ex vivo IFNγ ELISpot assay (methods) using OLP pools containing peptides that were 15 amino acids in length and spanning both S subunits (Spike pool 1-2, 3-4 \[S1\], 5-6, and 7-8 \[S2\]) and TCE regions Nuc and ORF3a/Membrane. Immunogenicity response was defined as \>= 2-fold change in levels from baseline. Response rate to both Spike pools (Spike pool 1-2, 3-4, 5-6, and 7-8) and TCE pools (Nuc OLP and ORF3a/Membrane OLP) was assessed.

Time frame: Baseline to 478 days