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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
581
ARCT-021 higher dose (one dose) + placebo (one dose)
ARCT-021 lower dose (two doses, Day 0 and Day 28)
ARCT-021 higher dose (two doses, Day 0 and Day 28)
Arcturus Investigational Site 103
Chandler, Arizona, United States
Arcturus Investigational Site 107
Tucson, Arizona, United States
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination
Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Booster Vaccination
Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: For 7 days following each dose administration (Day 208 up to Day 215)
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Each Priming Vaccination
Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Booster Vaccination
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Placebo (two doses, Day 0 and Day 28)
ARCT-021 (single dose) OR placebo, booster
Placebo (single dose)
Arcturus Investigational Site 112
San Diego, California, United States
Arcturus Investigational Site 104
Melbourne, Florida, United States
Arcturus Investigational Site 105
Orlando, Florida, United States
Arcturus Investigational Site 106
Pinellas Park, Florida, United States
Arcturus Investigational Site 109
The Villages, Florida, United States
Arcturus Investigational Site 101
Peoria, Illinois, United States
Arcturus Investigational Site 110
Rockville, Maryland, United States
Arcturus Investigational Site 102
Anderson, South Carolina, United States
...and 5 more locations
Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: For 7 days post booster dose administration (Day 208 up to Day 215)
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Each Priming Vaccination
An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: 28 days following each dose administration (Day 0 up to Day 28 for Vaccination 1 and Day 29 up to Day 56 for Vaccination 2)
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Booster Vaccination
An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: 28 days following each dose administration (Day 208 up to 236 days)
Percentage of Participants Reporting Treatment-Emergent Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE) and New Onset of Chronic Disease (NOCD) Post Each Priming Vaccination
SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as any AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Up to Day 207
Percentage of Participants Reporting Treatment-emergent Serious Adverse Events, Medically Attended Adverse Events and New Onset of Chronic Disease Post Booster Vaccination
SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as an AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 208 to early termination (up to 396 days)
Geometric Mean Titer (GMT) of Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies Post Priming Vaccination
Time frame: Day 1
GMT of SARS-CoV-2 Neutralizing Antibodies Post Priming Vaccination
Time frame: Day 56
GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination
Time frame: Day 208
GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination
Time frame: Day 236
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Priming Vaccination
GMFR is reported as a ratio to baseline (Day 0).
Time frame: Day 56
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
GMFR is reported as a ratio to baseline (Day 0).
Time frame: Day 208
GMFR in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
GMFR is reported as a ratio to baseline (Day 0).
Time frame: Day 236
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 56
Time frame: Baseline up to Day 56
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 208
Time frame: Baseline up to Day 208
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 236
Time frame: Baseline up to Day 236
Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Priming Vaccination
Time frame: Days 0 and 56
Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Booster Vaccination
Time frame: Day 208 and 236
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Before Vaccination to Day 56
Time frame: Day 56
Percentage of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels
Time frame: Day 56