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

NCT ID: NCT05148962

Last Updated: 2024-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-16
• Study Completion Date: 2023-05-26

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.

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

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cohort 1: GRT-R910 10 µg, age ≥60 years (Receipt of AstraZeneca vaccine)

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.

Group Type: EXPERIMENTAL

GRT-R910

Intervention Type: BIOLOGICAL

Injection administered intramuscularly

Cohort 2: GRT-R910 30 µg, age ≥60 years (Receipt of AstraZeneca vaccine)

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.

Group Type: EXPERIMENTAL

GRT-R910

Intervention Type: BIOLOGICAL

Injection administered intramuscularly

Cohort 3: GRT-R910 10 µg, ≥60 years, (Receipt of AstraZeneca or Janssen COVID-19 vaccine)

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.

Group Type: EXPERIMENTAL

GRT-R910

Intervention Type: BIOLOGICAL

Injection administered intramuscularly

Cohort 4: GRT-R910 10 µg, ≥60 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine)

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.

Group Type: EXPERIMENTAL

GRT-R910

Intervention Type: BIOLOGICAL

Injection administered intramuscularly

Cohort 6: GRT-R910 10 µg, ≥18 to ≤59 years, (Receipt of Pfizer/BioNTech, Moderna COVID-19 vaccine)

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.

Group Type: EXPERIMENTAL

GRT-R910

Intervention Type: BIOLOGICAL

Injection administered intramuscularly

Interventions

GRT-R910

Injection administered intramuscularly

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gritstone bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Martin, DO

Role: STUDY_DIRECTOR

Gritstone bio, Inc.

Locations

University Hospitals Birmingham NHS

Birmingham, , United Kingdom

University Hospital of Leicester NHS Trust

Leicester, , United Kingdom

Manchester University

Manchester, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37280238 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GO-009

Identifier Type: -

Identifier Source: org_study_id