COVID-19
Conditions
Brief summary
This is a multicenter, observer-blind, randomized, controlled phase 3 study to evaluate the immunogenicity, reactogenicity, and safety of an investigational self-amplifying RNA COVID-19 vaccine (ARCT-2303) administered concomitantly with quadrivalent influenza vaccines or standalone in adults who previously received authorized COVID-19 vaccine.
Detailed description
Approximately 1680 participants previously vaccinated with authorized COVID-19 vaccine will be enrolled in this study in two age cohorts (younger adults and older adults). Within each cohort, participants will be randomly assigned in a ratio of 1:1:1 to receive the ARCT-2303 vaccine concomitantly with a quadrivalent influenza vaccine, the ARCT-2303 vaccine and placebo, or the quadrivalent influenza vaccine and placebo. The assessment of immunogenicity will be performed 28 days after vaccination. To provide equal benefit from the participation in the study and complete seasonal vaccination against COVID-19 and influenza, a switchover vaccine dose (influenza, ARCT-2303 or placebo) will be administered 28 days after initial vaccination. All participants will be followed up for safety assessment until the end of the study. A historical control group vaccinated on a similar schedule (ARCT-154 vaccine) from a previous study (ARCT-154-J01) will be used to compare with the immunogenicity of the ARCT-2303 vaccine. Cohort A (younger adults; approximately 1200 participants): * Group 1a (ARCT-2303/Influenza vaccine): participants will receive one dose of ARCT-2303 and one dose of Influenza vaccine (opposite arms) on Day 1, and one dose of placebo on Day 29. * Group 2a (ARCT-2303): participants will receive one dose of ARCT-2303 and one dose of placebo (opposite arms) on Day 1, and one dose of Influenza vaccine on Day 29. * Group 3a (Influenza vaccine): participants will receive one dose of Influenza vaccine and one dose of placebo (opposite arms) on Day 1, and one dose of ARCT-2303 on Day 29. Cohort B (older adults; approximately 480 participants): * Group 1b (ARCT-2303/Influenza vaccine): participants will receive one dose of ARCT-2303 and one dose of Influenza vaccine (opposite arms) on Day 1, and one dose of placebo on Day 29. * Group 2b (ARCT-2303): participants will receive one dose of ARCT-2303 and one dose of placebo (opposite arms) on Day 1, and one dose of Influenza vaccine on Day 29. * Group 3b (Influenza vaccine): participants will receive one dose of Influenza vaccine and one dose of placebo (opposite arms) on Day 1, and one dose of ARCT-2303 on Day 29.
Interventions
BIOLOGICALARCT-2303
Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)
BIOLOGICALInfluenza vaccine
Licensed cell-based influenza vaccine
BIOLOGICALInfluenza vaccine, adjuvanted
Licensed influenza vaccine, adjuvanted
OTHERPlacebo
0.9% saline
Sponsors
Seqirus
Novotech (Australia) Pty Limited
Arcturus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1, Individuals are male, female, or transgender adults ≥18 years of age. 2\. Healthy participants or participants with pre-existing stable medical conditions. 3\. Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed. 4\. Individuals must have been previously vaccinated with COVID-19 vaccines. 5\. Individuals of childbearing potential must be willing to adhere to contraceptive requirements.
Exclusion criteria
1. Individuals with acute medical illness or febrile illness. 2. Individuals with a positive SARS-CoV-2 rapid antigen test at Screening. 3. Individuals with a history of COVID-19 or virologically confirmed SARS-CoV-2 infection within the past 5 months or history of COVID-19 with ongoing sequelae. 4. Individuals with a known history of severe hypersensitivity reactions, including anaphylaxis, or other significant adverse reactions to any components of mRNA vaccine, or influenza vaccine, including egg protein. 5. Individuals who have a positive pregnancy test at the Screening visit or who intend to become pregnant or breastfeed during the study. 6. Individuals with a history of myocarditis, pericarditis, myopericarditis or cardiomyopathy. 7. Individuals with a history of Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis. 8. Individuals with a history of congenital or acquired immunodeficiency. 9. Individuals who have received immunomodulatory, immunostimulatory, or immunosuppressant drugs within 3 months of Screening; or individuals requiring systemic corticosteroids exceeding 10 mg/day of prednisone equivalent for ≥10 days within 30 days of Screening. 10. Individuals who have received immunoglobulins and/or any blood or blood products within the 3 months before the first vaccine administration or plan to receive such products at any time during the study. 11. Individuals with a documented history of HIV infection, or who are currently known to have active tuberculosis. 12. Individuals receiving treatment with another investigational drug, biological agent, or device. 13. Individuals who have received any investigational COVID-19 vaccines. 14. Individuals who received any influenza vaccine within 6 months prior to enrollment or plan to receive an influenza vaccine during the study period. 15. Individuals who have received any other licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the study vaccination. 16. Individuals who are investigator site staff members, employees of the Sponsor or the Clinical Research Organization 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29 | Day 29 | — |
| Groups 2a and 2b and ARCT-154-J01 Historical Control: Number of Participants With Seroconversion to SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | Day 29 | Seroconversion was defined as either a pre-vaccination titer below the lower limit of quantitation (LLOQ) and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. |
| Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | Day 29 | Influenza vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | Day 29 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | Day 29 | Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | Days 1 and 29 | Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Group 1a: Days 1 and 29; Group 2a: Days 1, 29, and 181 | — |
| Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Group 1a: Day 29; Group 2a: Days 29 and 181 | GMFR is reported as a ratio to Day 1. |
| Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | Day 29 | Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. |
| Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Days 1 and 29 | — |
| Groups 1b and 2b: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | Day 29 | Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. |
| Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | Days 1 and 29 | Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | Days 1 and 29 | Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | Day 29 | Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMFR is reported as a ratio to Day 1. |
| Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | Day 29 | Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | Days 1 and 29 | Vaccine strains analyzed for this outcome measure were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. |
| Number of Participants With Local and Systemic Adverse Events (AEs) | Day 8 and Day 36 (up to 7 days after each study vaccination) | Systemic AEs: fatigue, headache, myalgia, arthralgia, nausea, dizziness, chills, and fever. Solicited local (injection site) AEs: injection site pain, erythema, and swelling. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Unsolicited AEs | Up to Day 29 (Up to 28 days after first study vaccination) and up to Day 57 (28 days after second study vaccination) | An unsolicited AE was an AE that was not listed as 'solicited' and was defined as any spontaneously occurring AE (serious and non-serious). Potential unsolicited AEs may have been medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a healthcare provider) or were of concern to the participants. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | Day 1 up to Day 181 | 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, a congenital anomaly or birth defect, or was an important medical event. A MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. AESIs were defined as AEs potentially associated with Coronavirus Disease 2019 (COVID-19) and COVID-19 vaccines. Number of participants with AEs leading to early termination included AEs leading to death. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Days 1 and 29 | — |
| Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Group 1b: Days 1 and 29, Group 2b: Days 1, 29 and 181 | — |
| Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | Day 29 | Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMFR is reported as a ratio to Day 1. |
| Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Group 1b: Day 29 and Group 2b: Days 29 and 181 | GMFR is reported as a ratio to Day 1. |
Countries
Australia, Costa Rica, Honduras, Philippines
Participant flow
Pre-assignment details
This study utilized the study group (ARCT-154 vaccine) from study ARCT-154-J01 as a historical control. The participants in the historical control arm were not considered enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Group 1a: ARCT-2303+ QIV + Placebo Younger adult participants received one dose of ARCT-2303 and one dose of QIV on Day 1, and one dose of placebo on Day 29. | 403 |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV Younger adult participants received one dose of ARCT-2303 and one dose of placebo on Day 1, and one dose of QIV on Day 29. | 403 |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 Younger adult participants received one dose of QIV and one dose of placebo on Day 1, and one dose of ARCT-2303 on Day 29. | 398 |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo Older adult participants received one dose of ARCT-2303 and one dose of aQIV on Day 1, and one dose of placebo on Day 29. | 99 |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV Older adult participants received one dose of ARCT-2303 and one dose of placebo on Day 1, and one dose of aQIV on Day 29. | 98 |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 Older adult participants received one dose of aQIV and one dose of placebo on Day 1, and one dose of ARCT-2303 on Day 29. | 98 |
| ARCT-154-J01 (Historical Control) Participants from study ARCT-154-J01 with available pre- and post-vaccination serum samples who were allocated in the ARCT-154 group. This group of participants was used as a historical control group. | 385 |
| Total | 1,884 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 11 | 10 | 8 | 0 | 0 | 0 | 0 |
| Overall Study | Other than Specified | 1 | 0 | 4 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 8 | 4 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | ARCT-154-J01 (Historical Control) | Total | Cohort A Group 1a: ARCT-2303+ QIV + Placebo | Cohort A Group 2a: ARCT-2303 + Placebo + QIV | Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Cohort B Group 3b: aQIV + Placebo + ARCT-2303 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 11.9 | 44.2 years STANDARD_DEVIATION 16.9 | 37.7 years STANDARD_DEVIATION 12 | 36.8 years STANDARD_DEVIATION 12.1 | 39.2 years STANDARD_DEVIATION 11.9 | 69.6 years STANDARD_DEVIATION 5.3 | 70.4 years STANDARD_DEVIATION 5.4 | 70.4 years STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 255 Participants | 65 Participants | 67 Participants | 64 Participants | 23 Participants | 15 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 385 Participants | 1619 Participants | 333 Participants | 333 Participants | 332 Participants | 76 Participants | 83 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 10 Participants | 5 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 60 Participants | 18 Participants | 11 Participants | 16 Participants | 4 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 385 Participants | 1085 Participants | 150 Participants | 159 Participants | 177 Participants | 69 Participants | 77 Participants | 68 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 54 Participants | 14 Participants | 15 Participants | 13 Participants | 7 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 12 Participants | 7 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 133 Participants | 34 Participants | 42 Participants | 30 Participants | 10 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) White | 0 Participants | 537 Participants | 179 Participants | 173 Participants | 158 Participants | 9 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Female | 228 Participants | 1180 Participants | 259 Participants | 255 Participants | 243 Participants | 64 Participants | 68 Participants | 63 Participants |
| Sex: Female, Male Male | 157 Participants | 704 Participants | 144 Participants | 148 Participants | 155 Participants | 35 Participants | 30 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 403 | 0 / 403 | 0 / 398 | 0 / 99 | 0 / 98 | 1 / 98 |
| other Total, other adverse events | 65 / 403 | 59 / 403 | 49 / 398 | 6 / 99 | 0 / 98 | 14 / 98 |
| serious Total, serious adverse events | 7 / 403 | 5 / 403 | 6 / 398 | 2 / 99 | 3 / 98 | 5 / 98 |
Outcome results
Primary
Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | 768 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | 954 titers |
Primary
Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29
Influenza vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 338 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 280 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | B/Victoria | 109 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 123 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 112 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 354 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | B/Victoria | 99 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 269 titers |
Primary
Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29
Time frame: Day 29
Population: Study treatment arm: per protocol (PP) set for immunogenicity, participants in the Modified Intent-To-Treat Analysis Set (mITT) who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29 or Day 181) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. As pre-specified, data for groups 2a \& 2b were collected and are reported pooled as a combined group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29 | 718 Titer |
| ARCT-154-J01 (Historical Control) | Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29 | 263 Titer |
Primary
Groups 2a and 2b and ARCT-154-J01 Historical Control: Number of Participants With Seroconversion to SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29
Seroconversion was defined as either a pre-vaccination titer below the lower limit of quantitation (LLOQ) and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer.
Time frame: Day 29
Population: Study treatment arm: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. As pre-specified, data for groups 2a \&2b were collected and are reported pooled as a combined group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 2a and 2b and ARCT-154-J01 Historical Control: Number of Participants With Seroconversion to SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | 349 Participants |
| ARCT-154-J01 (Historical Control) | Groups 2a and 2b and ARCT-154-J01 Historical Control: Number of Participants With Seroconversion to SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29 | 175 Participants |
Secondary
Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181
GMFR is reported as a ratio to Day 1.
Time frame: Group 1a: Day 29; Group 2a: Days 29 and 181
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29 or Day 181) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. Overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 29 | 6.7 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 29 | 7.7 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 181 | 5.3 ratio |
Secondary
Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181
Time frame: Group 1a: Days 1 and 29; Group 2a: Days 1, 29, and 181
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29 or Day 181) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. Overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 1 | 118 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 29 | 789 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 1 | 140 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 29 | 1072 titers |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 181 | 794 titers |
Secondary
Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 1 | 331 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 29 | 375 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 1 | 344 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 29 | 378 Participants |
Secondary
Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29
Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | 242 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | 279 Participants |
Secondary
Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29
Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMFR is reported as a ratio to Day 1.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 11.2 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 10.3 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 8.1 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 4.6 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 3.7 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 11.6 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 6.9 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 9.2 ratio |
Secondary
Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29
Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 29 | 331 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 1 | 38 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 29 | 429 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 1 | 32 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 1 | 13 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 29 | 109 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 1 | 29 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 29 | 132 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 29 | 126 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 1 | 15 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 1 | 37 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 1 | 34 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 29 | 433 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 29 | 102 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 1 | 36 titer |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 29 | 334 titer |
Secondary
Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29
Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 1 | 197 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 29 | 354 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 1 | 178 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 29 | 361 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 1 | 73 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 29 | 299 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 1 | 165 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 29 | 345 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 29 | 347 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 1 | 195 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 1 | 83 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 29 | 367 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 1 | 201 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 1 | 200 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 29 | 294 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 29 | 364 Participants |
Secondary
Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29
Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 267 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 266 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 233 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 197 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 167 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 259 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 215 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 266 Participants |
Secondary
Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181
GMFR is reported as a ratio to Day 1.
Time frame: Group 1b: Day 29 and Group 2b: Days 29 and 181
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29 or Day 181) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. Overall number of participants analyzed = number evaluable for the outcome measure. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 29 | 6.8 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 29 | 6.9 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181 | Day 181 | 4.3 ratio |
Secondary
Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181
Time frame: Group 1b: Days 1 and 29, Group 2b: Days 1, 29 and 181
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29 or Day 181) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data. Overall number of participants analyzed = number evaluable for the outcome measure. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 1 | 138 titer |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 29 | 932 titer |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 1 | 206 titer |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 29 | 1420 titer |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181 | Day 181 | 878 titer |
Secondary
Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 1 | 84 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 29 | 92 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 1 | 90 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29 | Day 29 | 95 Participants |
Secondary
Groups 1b and 2b: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29
Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 2b: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | 66 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 2b: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29 | 70 Participants |
Secondary
Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29
Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMFR is reported as a ratio to Day 1.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 9.2 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 6.0 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 6.2 ratio |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 5.5 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 5.0 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 8.8 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 4.6 ratio |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 4.9 ratio |
Secondary
Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29
Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 1 | 115 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 29 | 1064 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 1 | 78 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 29 | 475 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 1 | 20 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 29 | 121 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 1 | 25 titers |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 29 | 138 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 29 | 132 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 1 | 109 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 1 | 29 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H1N1 Day 29 | 961 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Yamagata Day 1 | 27 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 1 | 92 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | B/Victoria Day 29 | 132 titers |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29 | A/H3N2 Day 29 | 453 titers |
Secondary
Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29
Vaccine strains analyzed for this outcome measure were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Days 1 and 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 1 | 75 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 29 | 92 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 1 | 62 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 29 | 90 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 1 | 32 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 29 | 76 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 1 | 37 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 29 | 84 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 29 | 81 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 1 | 71 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 1 | 41 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H1N1 Day 29 | 93 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Yamagata Day 1 | 40 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 1 | 70 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | B/Victoria Day 29 | 80 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29 | A/H3N2 Day 29 | 91 Participants |
Secondary
Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29
Seroconversion was defined as either a pre-vaccination titer below the LLOQ and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer. Vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Time frame: Day 29
Population: PP set for immunogenicity, which included participants in the mITT who correctly received all protocol-required doses of study vaccines at Day 1 and who at or prior to the specified timepoint (Day 29) had no evidence of SARS-CoV-2 infection and no protocol deviations impacting the analysis of immunogenicity data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 59 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 50 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 47 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 48 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Yamagata | 47 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H1N1 | 59 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | B/Victoria | 45 Participants |
| ARCT-154-J01 (Historical Control) | Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29 | A/H3N2 | 42 Participants |
Secondary
Number of Participants With Local and Systemic Adverse Events (AEs)
Systemic AEs: fatigue, headache, myalgia, arthralgia, nausea, dizziness, chills, and fever. Solicited local (injection site) AEs: injection site pain, erythema, and swelling. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 8 and Day 36 (up to 7 days after each study vaccination)
Population: Safety Analysis Set (SAF), which included all participants in the Exposed Set (participants who received at least one dose of a study vaccine) who provided any evaluable post-vaccination reactogenicity and/or safety data. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 283 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 105 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 38 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 255 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 118 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 258 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 296 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 146 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 263 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 162 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 167 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 217 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 5 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 36 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 41 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 14 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 15 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 23 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 30 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 15 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after Second Vaccination (up to Day 36) | 17 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after First Vaccination (up to Day 8) | 20 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Systemic AE after First Vaccination (up to Day 8) | 25 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Local and Systemic Adverse Events (AEs) | Solicited Local AE after Second Vaccination (up to Day 36) | 22 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs)
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, a congenital anomaly or birth defect, or was an important medical event. A MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. AESIs were defined as AEs potentially associated with Coronavirus Disease 2019 (COVID-19) and COVID-19 vaccines. Number of participants with AEs leading to early termination included AEs leading to death. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 1 up to Day 181
Population: Safety Analysis Set, which included all participants in the Exposed Set (participants who received at least one dose of a study vaccine) who provided any evaluable post-vaccination reactogenicity and/or safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 7 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 0 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 103 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 1 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 95 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 1 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 5 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 1 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 3 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 100 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 0 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 6 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 2 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 1 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 0 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 19 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 13 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 1 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 0 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 3 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AEs Leading to Early Termination from Study | 1 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | MAAEs | 19 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | AESIs | 1 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs) | SAEs | 5 Participants |
Secondary
Number of Participants With Unsolicited AEs
An unsolicited AE was an AE that was not listed as 'solicited' and was defined as any spontaneously occurring AE (serious and non-serious). Potential unsolicited AEs may have been medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a healthcare provider) or were of concern to the participants. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Up to Day 29 (Up to 28 days after first study vaccination) and up to Day 57 (28 days after second study vaccination)
Population: Safety Analysis Set, which included all participants in the Exposed Set (participants who received at least one dose of a study vaccine) who provided any evaluable post-vaccination reactogenicity and/or safety data. Overall number of participants analyzed = participants evaluable for the outcome measure. Number analyzed = participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Unsolicited AEs | Day 57 | 71 Participants |
| Cohort A Group 2a: ARCT-2303 + Placebo + QIV and Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Unsolicited AEs | Day 29 | 79 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Unsolicited AEs | Day 57 | 62 Participants |
| ARCT-154-J01 (Historical Control) | Number of Participants With Unsolicited AEs | Day 29 | 81 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Unsolicited AEs | Day 29 | 68 Participants |
| Cohort A Group 3a: QIV + Placebo + ARCT-2303 | Number of Participants With Unsolicited AEs | Day 57 | 75 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Unsolicited AEs | Day 29 | 13 Participants |
| Cohort B Group 1b: ARCT-2303 + Adjuvanted QIV (aQIV) + Placebo | Number of Participants With Unsolicited AEs | Day 57 | 9 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Unsolicited AEs | Day 29 | 8 Participants |
| Cohort B Group 2b: ARCT-2303 + Placebo + aQIV | Number of Participants With Unsolicited AEs | Day 57 | 6 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Unsolicited AEs | Day 57 | 17 Participants |
| Cohort B Group 3b: aQIV + Placebo + ARCT-2303 | Number of Participants With Unsolicited AEs | Day 29 | 16 Participants |