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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
1,514
Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)
Licensed cell-based influenza vaccine
Licensed influenza vaccine, adjuvanted
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
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
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
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
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
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
Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29
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0.9% saline
Paratus Clinical Canberra
Canberra, Australian Capital Territory, Australia
Paratus Clinical Central Coast
Central Coast, New South Wales, Australia
Sutherland Shire Clinical Research - Walski
Miranda, New South Wales, Australia
Australian Clinical Research Network (ACRN)
Sydney, New South Wales, Australia
Austrials - St. Leonards
Sydney, New South Wales, Australia
Emeritus Research Sydney
Sydney, New South Wales, Australia
Griffith University Clinical Trials Unit
Sydney, New South Wales, Australia
Northern Beaches Clinical Research - Walski
Sydney, New South Wales, Australia
Paratus Clinical Blacktown
Sydney, New South Wales, Australia
Wollongong Clinical Research
Wollongong, New South Wales, Australia
...and 19 more locations
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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