COVID-19Phase 1NCT05148962
Study of GRT-R910 COVID-19 Boost Vaccine in Healthy Volunteers
A Phase 1 study testing GRT-R910 in people with COVID-19, run by Gritstone bio, Inc. at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19
- What is being tested?
- GRT-R910
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 16 Sep 2021to 26 May 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University Hospitals Birmingham NHS
Birmingham
University Hospital of Leicester NHS Trust
Leicester
Manchester University
Manchester
About this study
Official title: A Phase 1 Trial to Evaluate the Safety, Immunogenicity, and Reactogenicity of a Self-Amplifying mRNA Prophylactic Vaccine Boost Against SARS-CoV-2 in Previously Vaccinated Healthy Adults 18 Years and Older
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.
Read the detailed description
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).
- Conditions
- COVID-19
- Being tested
- GRT-R910
- Keywords
- SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRT-R910Biological
Injection administered intramuscularly
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: GRT-R910 10 µg, age ≥60 years (Receipt of AstraZeneca vaccine) | Experimental | Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 10 microgram (µg) intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months. Receives: Biological: GRT-R910 |
| Cohort 2: GRT-R910 30 µg, age ≥60 years (Receipt of AstraZeneca vaccine) | Experimental | Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 30 µg intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg, which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months. Receives: Biological: GRT-R910 |
| Cohort 3: GRT-R910 10 µg, ≥60 years, (Receipt of AstraZeneca or Janssen COVID-19 vaccine) | Experimental | Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving an adenoviral COVID-19 (AstraZeneca, Janssen) primary series vaccine. Participants were followed for 13 months. Receives: Biological: GRT-R910 |
| Cohort 4: GRT-R910 10 µg, ≥60 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine) | Experimental | Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving a messenger ribonucleic acid (mRNA)-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months. Receives: Biological: GRT-R910 |
| Cohort 6: GRT-R910 10 µg, ≥18 to ≤59 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine) | Experimental | Healthy participants of age ≥18 to ≤59 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving mRNA-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months. Receives: Biological: GRT-R910 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Baseline, Day 120
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Cohorts 3, 4, and 6
Measured: Baseline, Day 8
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 37 in Cohorts 3, 4, and 6
Measured: Baseline, Day 37
Change From Baseline in Hemoglobin at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 120
Change From Baseline in Hemoglobin at Day 8 in Cohorts 3, 4, and 6
Measured: Baseline, Day 8
Change From Baseline in Hemoglobin at Day 37 in Cohorts 3, 4, and 6
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Baseline, Day 120
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Cohorts 3, 4, and 6
Measured: Baseline, Day 8
Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 37 in Cohorts 3, 4, and 6
Measured: Baseline, Day 37
Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 120
Change From Baseline in Bilirubin and Creatinine at Day 8 in Cohorts 3, 4, and 6
Measured: Baseline, Day 8
Change From Baseline in Bilirubin and Creatinine at Day 37 in Cohorts 3, 4, and 6
Measured: Baseline, Day 37
Change From Baseline in Creatine Kinase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
Measured: Baseline, Day 120
Change From Baseline in Creatine Kinase at Day 8 in Cohorts 3, 4, and 6
Measured: Baseline, Day 8
Change From Baseline in Creatine Kinase at Day 37 in Cohorts 3, 4, and 6
Measured: 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.
Measured: Day 1 Up to 16 months
Secondary outcomes (7)
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).
Measured: 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.
Measured: 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.
Measured: 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]).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 478 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2021
- Study start16 Sep 2021
- Primary completion26 May 2023
- Study completion26 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gritstone bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Elizabeth Martin, DO, Study director, Gritstone bio, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05148962
- Sponsor's protocol ID
- GO-009
- Status last verified
- Dec 2024
- First submitted
- 3 Dec 2021
- Last updated
- 11 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palmer CD, Scallan CD, Kraemer Tardif LD, Kachura MA, Rappaport AR, Koralek DO, Uriel A, Gitlin L, Klein J, Davis MJ, Venkatraman H, Hart MG, Jaroslavsky JR, Kounlavouth S, Marrali M, Nganje CN, Bae K, Yan T, Leodones K, Egorova M, Hong SJ, Kuan J, Grappi S, Garbes P, Jooss K, Ustianowski A. GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for >/=6 months in previously-vaccinated older adults. Nat Commun. 2023 Jun 6;14(1):3274. doi: 10.1038/s41467-023-39053-9.
PubMed 37280238
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial to Evaluate the Safety, Immunogenicity, and Reactogenicity of a Self-Amplifying mRNA Prophylactic Vaccine Boost Against SARS-CoV-2 in Previously Vaccinated Healthy Adults 18 Years and Older
- ClinicalTrials.gov ID
- NCT05148962
- Acronym / sponsor ID
- GO-009
- Conditions
- COVID-19
- Keywords
- SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Gritstone bio, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Sep 2021 (actual)
- Primary completion
- 26 May 2023 (actual)
- Study completion
- 26 May 2023 (actual)
- First posted
- 8 Dec 2021 (actual)
- Results
- Posted 11 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: GRT-R910 10 µg, age ≥60 years (Receipt of AstraZeneca vaccine) | Experimental | Biological: GRT-R910Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 10 microgram (µg) intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months. |
| Cohort 2: GRT-R910 30 µg, age ≥60 years (Receipt of AstraZeneca vaccine) | Experimental | Biological: GRT-R910Healthy participants of age ≥60 years received prime dose (on Day 1) of GRT-R910 30 µg intramuscularly at least 2 months after receiving a first-generation COVID-19 (AstraZeneca) vaccine primary series. A subset of participants elected to receive a booster vaccination of GRT-R910 10 µg, which was administered 113 days after the prime vaccination. Participants not receiving booster dose were followed for 12 months, and participants receiving booster dose were followed for 16 months. |
| Cohort 3: GRT-R910 10 µg, ≥60 years, (Receipt of AstraZeneca or Janssen COVID-19 vaccine) | Experimental | Biological: GRT-R910Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving an adenoviral COVID-19 (AstraZeneca, Janssen) primary series vaccine. Participants were followed for 13 months. |
| Cohort 4: GRT-R910 10 µg, ≥60 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine) | Experimental | Biological: GRT-R910Healthy participants of age ≥60 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving a messenger ribonucleic acid (mRNA)-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months. |
| Cohort 6: GRT-R910 10 µg, ≥18 to ≤59 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine) | Experimental | Biological: GRT-R910Healthy participants of age ≥18 to ≤59 years received two doses (Day 1 and Day 29) of GRT-R910 10 µg (homologous prime-boost), at least 2 months after receiving mRNA-based COVID-19 (Pfizer/BioNTech, Moderna) primary series vaccine. Participants were followed for 13 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRT-R910Injection administered intramuscularly | Biological | Cohort 1: GRT-R910 10 µg, age ≥60 years (Receipt of AstraZeneca vaccine), Cohort 2: GRT-R910 30 µg, age ≥60 years (Receipt of AstraZeneca vaccine), Cohort 3: GRT-R910 10 µg, ≥60 years, (Receipt of AstraZeneca or Janssen COVID-19 vaccine), Cohort 4: GRT-R910 10 µg, ≥60 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine), Cohort 6: GRT-R910 10 µg, ≥18 to ≤59 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine) |
Primary outcome
Number of Participants With at Least One Solicited Local Adverse Event (AE) Within 8 Days After the Injection of Prime Dose
Time frame: Within 8 Days After the Injection of Prime Dose on Day 1
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.
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)
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.
Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Prime Dose
Time frame: Within 8 Days After the Injection of Prime Dose on Day 1
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.
Number of Participants With at Least One Solicited Systemic 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)
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.
Number of Participants With at Least One Unsolicited Treatment-emergent AEs (TEAEs) Within 28 Days After the Injection of Prime Dose
Time frame: Within 28 Days After the Injection of Prime Dose on Day 1
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.
Number of Participants With at Least One Unsolicited TEAEs Within 28 Days After the Injection of Booster Dose
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)
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.
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)
Time frame: Day 1 Up to 16 months
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.
7 secondary outcomes
Change From Baseline in Immunoglobulin (Ig)G Level (Spike Wild Type [WT] Variant)
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
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
Time frame: Baseline to 478 days
Change From Baseline in T Cell Response by Spike Pools (ex Vivo ELISpot)
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)
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)
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)
Time frame: Baseline to 478 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37280238Palmer CD, Scallan CD, Kraemer Tardif LD, Kachura MA, Rappaport AR, Koralek DO, Uriel A, Gitlin L, Klein J, Davis MJ, Venkatraman H, Hart MG, Jaroslavsky JR, Kounlavouth S, Marrali M, Nganje CN, Bae K, Yan T, Leodones K, Egorova M, Hong SJ, Kuan J, Grappi S, Garbes P, Jooss K, Ustianowski A. GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for >/=6 months in previously-vaccinated older adults. Nat Commun. 2023 Jun 6;14(1):3274. doi: 10.1038/s41467-023-39053-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Martin, DO study director
Gritstone bio, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GRT-R910 in people with COVID-19, run by Gritstone bio, Inc. at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With at Least One Solicited Local Adverse Event (AE) Within 8 Days After the Injection of Prime Dose (time frame: Within 8 Days After the Injection of Prime Dose on Day 1). The study lists 32 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05148962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.