Safety and Immunogenicity Study of SARS-CoV-2 Nanoparticle Vaccine (GBP510) Adjuvanted With or Without AS03 (COVID-19)

This is a first-in-human, Phase I/II, randomized, placebo-controlled, observer-blinded, age-escalating study to assess the safety, reactogenicity and immunogenicity of a SK SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with or without AS03 in healthy younger and older adults.

The purpose of this study is to assess the safety, reactogenicity and immunogenicity of the candidate vaccine administered twice with 28-day interval in healthy adults including older adults.

A total of 320 healthy younger and older adults will be enrolled to receive 2 doses of either one GBP510 formulation with AS03 (Test group 1 or 3), or without AS03 (Test group 2 or 4), or placebo saline (Placebo group). Test group 2 will only be included in Stage 1.

This study will consist of 2 stages, and a stepwise approach will be adopted as a safety precaution. Approximately 80 healthy adults aged 19 to 55 years will be enrolled and vaccinated first in Stage 1, and blinded safety data collected through 7 days after the last study vaccination will be reviewed by the sponsor, and then by the independent Data Safety Monitoring Board (DSMB) in an unblinded manner. Advancement to Stage 2 for further enrollment of 240 healthy younger and older adults aged 19 to 85 years will be determined if an acceptable safety profile is confirmed based on the sponsor and DSMB review. DSMB will recommend whether to proceed to the next stage or not, and DSMB may suggest discontinuation of the study or adjustment of dose and dosing regimen based on the safety review.

Eligibility Criteria:
Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

1. For Stage 1, participant must be 19 to 55 years of age inclusive, at the time of signing the informed consent.

   For Stage 2, participant must be 19 to 85 years of age inclusive, at the time of signing the informed consent

   Type of Participant and Disease Characteristics
2. Participants who are healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, and medical judgement of the investigator
3. Participants who are able to attend all scheduled visits and comply with all study procedures.

   Weight
4. Body mass index (BMI) within the range 18-30 kg/m2 at screening (inclusive)

   Sex and Contraceptive/Barrier Requirements
5. Female participants of childbearing potential must agree to be heterosexually inactive, or agree to consistently use at least one acceptable method of contraception from at least 4 weeks prior to the 1st study vaccination to 12 weeks after the last study vaccination
6. Female participants with a negative urine or serum pregnancy test at screening

   Informed Consent
7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. Any clinically significant respiratory symptoms (e.g. cough, sore throat), febrile illness (tympanic temperature \>38°C), or acute illness within 72 hours prior to the 1st study vaccination. A prospective participant should not be included until 72 hours after the condition has resolved.
2. History of virologically-confirmed COVID-19 disease, or definite or suspected exposure to anyone known to have SARS-CoV-2 infection
3. History of virologically-confirmed SARS or MERS disease
4. History of congenital, hereditary, acquired immunodeficiency, or autoimmune disease
5. Any positive test results for hepatitis B, C, or HIV at screening
6. History of bleeding disorder or thrombocytopenia which is contraindicating intramuscular vaccination in the investigator's opinion
7. History of hypersensitivity and severe allergic reaction (e.g. anaphylaxis, Guillain-Barre syndrome) to any vaccines or components of the study intervention
8. History of malignancy within 5 years prior to the 1st study vaccination
9. Significant chronic illness that, in the opinion of the investigator, might increase risk of severe COVID-19, or interfere with the evaluation of the study objectives (e.g. asthma, chronic pulmonary disease, cardiovascular disease, chronic liver disease, diabetes mellitus, uncontrolled hypertension, renal disorders)
10. History of, or planned surgery under general anesthesia from 1 year prior to the 1st study vaccination through the study period
11. Any other conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives (e.g. neurologic or psychiatric conditions)
12. Female participants who are pregnant or breastfeeding
13. (Only for Stage 1) Current smokers or a recent smoking history within 12 weeks prior to the 1st study vaccination. Occasional smokers who smoke up to 10 cigarettes per month may be allowed to participate at the investigator's discretion

    Prior/Concomitant therapy
14. Receipt of any medications or vaccinations intended to prevent COVID-19.
15. Receipt of any vaccine within 4 weeks prior to the 1st study vaccination or planned receipt of any vaccine from enrollment through 28 days after the last study vaccination (Visit 7), except for influenza vaccination, which may be received at least 2 weeks prior to the 1st study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines
16. Receipt of immunoglobulins and/or any blood or blood products within 12 weeks prior to the 1st study vaccination
17. Chronic use (more than 2 consecutive weeks) of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (≥10mg prednisone/day or equivalent for more than 2 consecutive weeks) within 12 weeks prior to the 1st vaccination. The use of topical and nasal glucocorticoids will be permitted.

    Prior/Concurrent Clinical Study Experience
18. Participation in another clinical study involving study intervention within 6 months prior to the 1st study vaccination, or concurrent, planned participation in another clinical study with study intervention during this study period.

    Other Exclusions
19. Investigators, or study staff who are directly involved in the conduct of this study or supervised by the investigator, and their respective family members.
20. Healthcare worker or emergency response personnel in an occupation with a high risk of exposure to SARS-CoV-2