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

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.

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.