A Trial Evaluating the Safety and Effects of an RNA Vaccine ARCT-021 in Healthy Adults

This is a Phase 2, randomized, placebo-controlled, and observer-blind study in healthy adults.

The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19:

As 2 doses (at two different dose levels), separated by 28 days or as 1 dose

In adults 18 years of age and older

This is a multiregional, multicenter, Phase 2, randomized, observer-blind study designed to evaluate the safety, reactogenicity, and immunogenicity of the study vaccine in younger and older adult participants. Enrolled participants will be randomly assigned to receive either study vaccine ARCT-021 or placebo (sterile saline).

Approximately 600 participants (300 each in younger \[18 to \<56 years of age in United States or 21 to \<56 years of age in Singapore\] and older \[≥56 years of age\] participants) will be enrolled (including at least 50% of participants in the older cohort ≥65 years of age). Participants will be stratified by age and then randomly assigned (3 ARCT-021:1 placebo) to receive 2 doses of study vaccine separated by 28 days. At 180 days after second study vaccination (Day 208), participants in Study Groups 1, 2, and 3 will be randomly assigned again to receive a single booster dose of study vaccine (randomly assigned as 1 ARCT-021:1 placebo). Study Group 4 will not be randomized but will receive 1 dose of placebo at Day 208. Study Groups are summarized in Table 1. Study vaccine will be administered in an observer-blind fashion. Participants will be followed for safety and immunogenicity through 180 days after booster vaccination (Day 388). At a subset of clinical sites, all enrolled participants will also undergo blood sampling for evaluation of CMI responses.

Vaccine doses will be assigned as follows:

Younger Age Cohort:

Study Group 1: n= 75 participants, ARCT-021 7.5 µg (first dose), Placebo (second dose Study Group 2: n= 75 participants, ARCT-021 5.0 µg (first dose), 5.0 µg (second dose) Study Group 3: n= 75 participants, ARCT-021 7.5 µg (first dose), 7.5 µg (second dose) Study Group 4: n= 75 participants, Placebo (first dose), Placebo (second dose)

Booster Vaccine:

Study Groups 1, 2, 3: 113 participants, ARCT-021 5.0 µg or 7.5 µg, 112 participants, Placebo Study Group 4: n= 75 participants, Placebo

Older Age Cohort:

Study Group 1: n= 75 participants, ARCT-021 7.5 µg (first dose), Placebo (second dose Study Group 2: n= 75 participants, ARCT-021 5.0 µg (first dose), 5.0 µg (second dose) Study Group 3: n= 75 participants, ARCT-021 7.5 µg (first dose), 7.5 µg (second dose) Study Group 4: n= 75 participants, Placebo (first dose), Placebo (second dose)

Booster Vaccine:

Study Groups 1, 2, 3: 113 participants, ARCT-021 5.0 µg or 7.5 µg, 112 participants, Placebo Study Group 4: n= 75 participants, Placebo

A DSMB will be in place to independently review the safety data of participants. Pausing Rules are also utilized in this study to reduce risk to study participants.

The expected duration of participation for an individual participant is approximately 14 months, inclusive of the Screening period.

Eligibility Criteria:
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 or female ≥18 or (in Singapore) ≥21 years of age
6. are medically stable

Exclusion Criteria:

Individuals who:

1. have had SARS-CoV-2 infection or COVID-19 disease.
2. have had cancer except for cancers that were treated and that have low risk of returning
3. have chronic kidney disease
4. have some chronic lung diseases
5. have some heart conditions
6. have compromised immune systems
7. are obese
8. have sickle cell disease or some other blood disorders
9. are current smokers and/or use illegal drugs
10. have Type 2 diabetics
11. are immunocompromised, immunodeficient or have had a transplant
12. have autoimmune disease
13. have other severe or uncontrolled diseases or disease that may interfere with the interpretation of the study
14. have a positive test for hepatitis B or C or human immunodeficiency virus
15. have had a severe reaction to previous investigational vaccines
16. have a fever or are feeling sick close to the time of the first vaccination of the study
17. have positive drug test at screening
18. are pregnant
19. are breastfeeding
20. have a bleeding disorder
21. have previously received an investigational coronavirus vaccine (SARS-CoV(1) or MERS) or who plan to be in other COVID-19 studies
22. have recently been vaccinated with other vaccines
23. have recently received blood products
24. who work at one of the clinic sites participating in this study, work at Arcturus, who work at other companies that monitor the study or close family members to the sites, Arcturus, or partners involved in study monitoring
25. other restrictions may apply