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

NCT05148962 | Completed Phase 1 Results

• 1 other identifier: GO-009
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

COVID-19

Keywords

SARS-CoV-2 vaccine; Coronavirus Disease (COVID-19)

Outcome Measures

Primary Outcomes (32)

• 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.

  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.

  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.

  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.

  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.

  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.

  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)

  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)

  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)

  Baseline, Day 120

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

  Baseline, Day 8

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

  Baseline, Day 37

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

  Baseline, Day 8

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

  Baseline, Day 8

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

  Baseline, Day 120

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

  Baseline, Day 8

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

  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)

  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)

  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)

  Baseline, Day 120

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

  Baseline, Day 8

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

  Baseline, Day 37

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

  Baseline, Day 8

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

  Baseline, Day 8

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

  Baseline, Day 120

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

  Baseline, Day 8

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

  Baseline, Day 37

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

  Baseline, Day 8

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

  Baseline, Day 8

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

  Baseline, Day 120

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

  Baseline, Day 8

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

  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.

  Day 1 Up to 16 months

Secondary Outcomes (7)

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

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

• Change From Baseline in Neutralizing Antibody (nAb) Levels

  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

  Baseline to 478 days

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

  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)

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

Study Arms (5)

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.

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.

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.

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.

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.

Biological: GRT-R910

Interventions

GRT-R910 BIOLOGICAL

Injection administered intramuscularly

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Gritstone bio, Inc.: lead

Study Sites (3)

University Hospitals Birmingham NHS

Birmingham, United Kingdom

Location

University Hospital of Leicester NHS Trust

Leicester, United Kingdom

Location

Manchester University

Manchester, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37280238 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

GRT-R910 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Elizabeth Martin, Vice President, Clinical Development Infectious Disease
• Organization: Gritstone bio, Inc.

clinicalstudies@gritstone.com

+1 (877) 520-2233

Study Officials

• Elizabeth Martin, DO

  Gritstone bio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: December 8, 2021
• Study Start: September 16, 2021
• Primary Completion: May 26, 2023
• Study Completion: May 26, 2023
• Last Updated: December 11, 2024
• Results First Posted: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)