Clinical trial NCT05148962: Study of GRT-R910 COVID-19 Boost Vaccine in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Keywords: SARS-CoV-2 vaccine
Coronavirus Disease (COVID-19)
Lead sponsor: Gritstone bio, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: Number of Participants With at Least One Solicited Local Adverse Event (AE) Within 8 Days After the Injection of Prime Dose
timeFrame: Within 8 Days After the Injection of Prime Dose on Day 1
measure: Number of Participants With at Least One Solicited Local AE Within 8 Days After the Injection of Booster Dose
timeFrame: 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)
measure: Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Prime Dose
timeFrame: Within 8 Days After the Injection of Prime Dose on Day 1
measure: Number of Participants With at Least One Solicited Systemic AE Within 8 Days After the Injection of Booster Dose
timeFrame: 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)
measure: Number of Participants With at Least One Unsolicited Treatment-emergent AEs (TEAEs) Within 28 Days After the Injection of Prime Dose
timeFrame: Within 28 Days After the Injection of Prime Dose on Day 1
measure: Number of Participants With at Least One Unsolicited TEAEs Within 28 Days After the Injection of Booster Dose
timeFrame: 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)
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 120
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 8 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 8
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes at Day 37 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 37
measure: Change From Baseline in Hemoglobin at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Hemoglobin at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Hemoglobin at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 120
measure: Change From Baseline in Hemoglobin at Day 8 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 8
measure: Change From Baseline in Hemoglobin at Day 37 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 37
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 120
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 8 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 8
measure: Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at Day 37 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 37
measure: Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Bilirubin and Creatinine at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Bilirubin and Creatinine at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 120
measure: Change From Baseline in Bilirubin and Creatinine at Day 8 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 8
measure: Change From Baseline in Bilirubin and Creatinine at Day 37 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 37
measure: Change From Baseline in Creatine Kinase at Day 8 in Participants Without Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Creatine Kinase at Day 8 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 8
measure: Change From Baseline in Creatine Kinase at Day 120 in Participants With Booster Dose (Cohorts 1 and 2)
timeFrame: Baseline, Day 120
measure: Change From Baseline in Creatine Kinase at Day 8 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 8
measure: Change From Baseline in Creatine Kinase at Day 37 in Cohorts 3, 4, and 6
timeFrame: Baseline, Day 37
measure: 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)
timeFrame: Day 1 Up to 16 months
Secondary outcomes:
measure: Change From Baseline in Immunoglobulin (Ig)G Level (Spike Wild Type [WT] Variant)
timeFrame: Baseline, Days 15, 29, 57, 58, 86, 113, 142, 180, 209, 293, 365, 394, 478
measure: Change From Baseline in Neutralizing Antibody (nAb) Levels
timeFrame: 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
measure: Number of Participants With Immunogenicity Response by Spike IgG and nAb Variants
timeFrame: Baseline to 478 days
measure: Change From Baseline in T Cell Response by Spike Pools (ex Vivo ELISpot)
timeFrame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478
measure: Change From Baseline in T Cell Response by T Cell Epitope (TCE) Pools (ex Vivo ELISpot)
timeFrame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293, 365, 478
measure: Change From Baseline in Immunogenicity Response by TCE Pools (in Vitro Stimulation)
timeFrame: Baseline, Days 8, 29, 58, 113, 142, 180, 209, 293
measure: Number of Participants With Immunogenicity Response by Spike Pools and TCE Pools (ex Vivo ELISpot)
timeFrame: Baseline to 478 days
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS
city: Leicester
country: United Kingdom
facility: University Hospital of Leicester NHS Trust
city: Manchester
country: United Kingdom
facility: Manchester University
Study officials:
affiliation: Gritstone bio, Inc.
name: Elizabeth Martin, DO
role: STUDY_DIRECTOR
References: