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

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

Detailed Description
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This trial will study a self-amplifying mRNA (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 SARS-CoV-2.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Biological: GRT-R910 10 mcg Dose (after AZ)
* Biological: GRT-R910 30 mcg Dose (after AZ)
* Biological: GRT-R910 10 mcg Dose (After Adenovirus based vaccine)
* Biological: GRT-R910 10 mcg Dose (after mRNA based vaccine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Cohorts 1 and 2, have received AstraZeneca's COVID-19 prime and boost vaccine at least 2 months prior to study participation. For Cohort 3, have previously received Janssen/Johnson and Johnson or AstraZeneca vaccine with or without booster dose(s) of an authorized vaccine at least 2 months prior to Day 1. For Cohorts 4 and 6, have previously received an mRNA COVID-19 vaccine with or without booster dose(s) of an authorized vaccine with the last dose received at least 2 months 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 participants 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. 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). Positive for SARS-CoV-2 by lateral flow test (rapid diagnostic test), enzyme-linked immunosorbent assay (ELISA) or by nasal swab polymerase chain reaction (PCR) at screening (Cohorts 3-6). 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. Any confirmed or suspected immunosuppressive or immunodeficient state. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 1 or 2 Doses of 10 mcg GRT-R910 after AstraZeneca Standard of Care<br>Healthy adults ≥60 years of age receive up to 2 doses of 10 mcg GRT-R910 homologous prime-boost | Biological: GRT-R910 10 mcg Dose (after AZ)<br>* 10 mcg vaccine by intramuscular (IM) injection on Day 1 (required) and on Day 113 (optional)<br>|
| Experimental: Cohort 2: 1 or 2 Doses of 30 mcg GRT-R910 after AstraZeneca Standard of Care<br>Healthy adults ≥60 years of age receive up to 2 doses of 30 mcg GRT-R910 homologous prime-boost | Biological: GRT-R910 30 mcg Dose (after AZ)<br>* 30 mcg vaccine by intramuscular (IM) injection on Day 1 (required) and on Day 113 (optional)<br>|
| Experimental: Cohort 3: 2 Doses 10 mcg GRT-R910 after Adenovirus-Based Vector Vaccine Standard of Care<br>Healthy adults ≥60 years of age receive 2 doses of 10 mcg GRT-R910 homologous prime-boost | Biological: GRT-R910 10 mcg Dose (After Adenovirus based vaccine)<br>* GRT-R910 10 mcg vaccine by intramuscular (IM) injection on Day 1 and on Day 29<br>|
| Experimental: Cohort 4: 2 Doses 10 mcg GRT-R910 after mRNA Vaccine Standard of Care<br>Healthy adults ≥60 years of age receive 2 doses of 10 mcg GRT-R910 homologous prime-boost | Biological: GRT-R910 10 mcg Dose (after mRNA based vaccine)<br>* GRT-R910 10 mcg vaccine by intramuscular (IM) injection on Day 1 and on Day 29<br>|
| Experimental: Cohort 6: 2 Doses 10 mcg GRT-R910 after mRNA Vaccine Standard of Care<br>Healthy adults ≥18 to ≤59 years of age receive 2 doses of 10 mcg GRT-R910 homologous prime-boost | Biological: GRT-R910 10 mcg Dose (after mRNA based vaccine)<br>* GRT-R910 10 mcg vaccine by intramuscular (IM) injection on Day 1 and on Day 29<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Solicited Local Reactogenicity Signs and Symptoms |  | Up to 7 days after each vaccination | 
| Number of Participants with One or More Solicited Systemic Reactogenicity Signs and Symptoms |  | Up to 7 days after each vaccination | 
| Number of Participants with One or More Unsolicited Adverse Events (AEs) |  | Up to 28 days after each vaccination | 
| Change from Baseline for Clinical Safety Laboratory Parameters |  | Up to 7 days after each vaccination | 
| Number of Participants with One or More Serious Adverse Events |  | Up to  16 months after each vaccination | 
| Number of Participants with One or More Adverse Events of Special Interest (AESIs) Including Potentially Immune-Mediated Medical Condition (PIMMCs), Medically Attended Adverse Events (MAAEs) and New Onset Chronic Medical Condition (NOCMCs) |  | Up to  16 months after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate and magnitude of SARS-CoV-2 Specific Antibody Binding and Neutralization Titers in Serum Samples [Time Frame: Up to  16 months after the prime vaccinationSerum Samples |  | Up to  16 months after prime vaccination | 
| Response Rate, magnitude, and breath of SARS-CoV-2 Specific T-Cells by Interferon-gamma (IFN-γ) Enzyme-Linked Immunospot (IFN-γ ELISpot) Assay |  | Up to  16 months after prime vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 vaccine, Coronavirus Disease (COVID-19)