A Trial Evaluating the Safety and Immunogenicity of 3 COVID-19 SARS-CoV-2 RNA Vaccines in Healthy Adults

A Phase 1/2 Randomized, Observer-Blind Study of the Safety, Reactogenicity, and Immunogenicity of 3 SARS-CoV-2 RNA Vaccine Candidates in Adults Previously Vaccinated and Not Previously Vaccinated Against SARS-CoV-2

This is a Phase 1/2, randomized, observer-blind study in healthy adults. The study will evaluate the safety, reactogenicity, and immunogenicity of 3 SARS-CoV-2 self-amplifying RNA vaccine candidates against COVID-19 in adults previously vaccinated and not previously vaccinated against SARS-CoV-2.

The study will initially enroll approximately 72 adult participants into 2 cohorts (A and B). Cohort A is further sub-divided into two sub-cohorts which include 12 participants who are seronegative, not previously vaccinated at screening (Sub-cohort A1) and 24 participants who are seropositive, not previously vaccinated at screening (Sub-cohort A2).

Within the first cohort (Cohort A), Sub-cohort A1 will include a total of 12 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Sub-cohort A2 will include a total of 24 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Study vaccines will be given as 2 doses separated by 28 days.

The second cohort (Cohort B) will include a total of 36 adult participants ≥21 to ≤65 years of age who have been previously vaccinated (5 months or longer prior to study enrollment) with SARS-CoV-2 vaccine. Study vaccines will be given as single doses.

Additional cohorts may increase the age range of participants up to 80 years of age.

Inclusion Criteria:

Individuals who:

1. Are able to provide consent
2. Agree to comply with all study visits and procedures
3. Are willing and able to adhere to study restrictions
4. Are sexually active and willing to adhere to contraceptive requirements
5. Are male, female, or transgender ≥21 to ≤80 years of age
6. For the previously vaccinated groups only, received 2 doses of SARS-CoV-2 vaccine 5 months or longer prior to study enrollment

Exclusion Criteria:

Individuals who:

1. For the unvaccinated groups only, previously received any investigational or authorized MERS-CoV, SARS-CoV, and SARS-CoV-2 vaccines (including ARCT-021)
2. For the previously vaccinated groups only, previously received BNT162b2 but have not received 2 doses within at least 5 months prior to study enrollment
3. Are planning to receive other COVID-19 vaccines during the study period
4. Recently received other vaccines
5. Have a fever or are feeling sick close to the time of the first study vaccination
6. Have a known history of COVID-19 disease or asymptomatic SARS-CoV-2 infection
7. Are pregnant or breastfeeding
8. Have had a severe reaction to previous vaccines
9. Have a severe or uncontrolled disease(s) that may interfere with the interpretation of the study
10. Have some respiratory diseases
11. Have some significant heart diseases
12. Have some neurological conditions
13. Have sickle cell disease or some other blood disorders
14. Have had a major surgery within the past 6 months
15. Have a history of chronic liver disease
16. Have a history of autoimmune disease or immunodeficiency
17. Have received allergy injections, interferon, immunomodulators, cytotoxic drugs or other similar toxic drugs.
18. Have received blood products
19. Have a positive test for hepatitis B or C or human immunodeficiency virus
20. Have uncontrolled hypertension
21. Have had cancer except for cancers that were treated and that have low risk of returning
22. Are obese
23. Are Investigator site staff members, employees of Arcturus or the contract research organization (CRO) directly involved in the conduct of the study, or site staff members otherwise supervised by the Investigator or immediate family members of any of the previously mentioned individuals