Immunogenicity and Safety Study of Self-amplifying MRNA COVID-19 Vaccine Administered with Influenza Vaccines in Adults
- Conditions
- COVID-19
- Interventions
- Biological: ARCT-2303Biological: Influenza vaccine, adjuvantedBiological: Influenza vaccineOther: Placebo
- Registration Number
- NCT06279871
- Lead Sponsor
- Arcturus Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1499
1, Individuals are male, female, or transgender adults ≥18 years of age.
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Healthy participants or participants with pre-existing stable medical conditions.
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Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
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Individuals must have been previously vaccinated with COVID-19 vaccines.
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Individuals of childbearing potential must be willing to adhere to contraceptive requirements.
- Individuals with acute medical illness or febrile illness.
- Individuals with a positive SARS-CoV-2 rapid antigen test at Screening.
- 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.
- 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.
- Individuals who have a positive pregnancy test at the Screening visit or who intend to become pregnant or breastfeed during the study.
- Individuals with a history of myocarditis, pericarditis, myopericarditis or cardiomyopathy.
- Individuals with a history of Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis.
- Individuals with a history of congenital or acquired immunodeficiency.
- 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.
- 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.
- Individuals with a documented history of HIV infection, or who are currently known to have active tuberculosis.
- Individuals receiving treatment with another investigational drug, biological agent, or device.
- Individuals who have received any investigational COVID-19 vaccines.
- Individuals who received any influenza vaccine within 6 months prior to enrollment or plan to receive an influenza vaccine during the study period.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1b (ARCT-2303/ Influenza vaccine) Influenza vaccine, adjuvanted Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 3a (Influenza vaccine) Placebo Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 1a (ARCT-2303/Influenza vaccine) ARCT-2303 Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 2a (ARCT-2303) Influenza vaccine Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29. Group 3b (Influenza vaccine) Influenza vaccine, adjuvanted Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 3b (Influenza vaccine) Placebo Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 2a (ARCT-2303) ARCT-2303 Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29. Group 2a (ARCT-2303) Placebo Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29. Group 2b (ARCT-2303) Placebo Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29. Group 3b (Influenza vaccine) ARCT-2303 Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 1b (ARCT-2303/ Influenza vaccine) Placebo Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 2b (ARCT-2303) ARCT-2303 Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29. Group 3a (Influenza vaccine) Influenza vaccine Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 1a (ARCT-2303/Influenza vaccine) Influenza vaccine Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 1a (ARCT-2303/Influenza vaccine) Placebo Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 3a (Influenza vaccine) ARCT-2303 Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29. Group 1b (ARCT-2303/ Influenza vaccine) ARCT-2303 Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29. Group 2b (ARCT-2303) Influenza vaccine, adjuvanted Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
- Primary Outcome Measures
Name Time Method SARS-CoV-2 neutralizing antibody titers Day 29 Immune response as measured by GMTs of neutralizing antibodies against Omicron XBB.1.5 subvariant (Group 1a; Group 2a)
SARS-CoV-2 neutralizing antibody seroconversion rates Day 29 Immune response as measured by SARS-CoV-2 neutralizing antibody seroconversion rates against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)
Hemagglutination Inhibition (HI) titers Day 1, Day 29 Immune response as measured by GMTs against influenza vaccine strains (Group 1a; Group 3a)
- Secondary Outcome Measures
Name Time Method SARS-CoV-2 neutralizing antibody titers Day 29 GMTs of SARS-CoV-2 neutralizing antibody titers against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)
SARS-CoV-2 neutralizing antibody responses Day 181 SARS-CoV-2 neutralizing antibody responses against Omicron XBB.1.5 subvariant as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with antibody titer ≥ LLOQ (Group 1b; Group 2b)
Hemagglutination Inhibition (HI) assay titers Day 29 HI assay titers against influenza vaccine strains as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with HI titers ≥1:40 (Group 1b; Group 3b)
SAE, Medically Attended Adverse Events (MAAE), Adverse Events of Special Interest (AESI), and AE leading to early termination Day 1 to Day 181 Proportion of participants with SAE/MAAE/AESI/AE leading to early termination from study
SARS-CoV-2 neutralizing antibody seroconversion rates Day 29 SARS-CoV-2 neutralizing antibody seroconversion rates against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)
SARS-CoV-2 neutralizing antibody response (Group 1a; Group 2a) Days 1, 29 and 181 SARS-CoV-2 neutralizing antibody responses against Omicron XBB.1.5 subvariant as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with antibody titer ≥ lower limit of quantitation (LLOQ) (Group 1a; Group 2a)
Hemagglutination Inhibition (HI) titers Day 1, Day 29 HI assay titers against influenza vaccine strains as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with HI titers ≥1:40 (Group 1a; Group 3a)
Local and systemic adverse events (AEs) Day 1 to Day 8 after each vaccination Proportion of participants with local and systemic solicited AEs
Unsolicited AEs Day 1 to Day 29 after each vaccination Proportion of participants with unsolicited AEs
Trial Locations
- Locations (29)
Paratus Clinical Central Coast
🇦🇺Central Coast, New South Wales, Australia
Australian Clinical Research Network (ACRN)
🇦🇺Sydney, New South Wales, Australia
Emeritus Research Sydney
🇦🇺Sydney, New South Wales, Australia
Northern Beaches Clinical Research - Walski
🇦🇺Sydney, New South Wales, Australia
USC Morayfield
🇦🇺Morayfield, Queensland, Australia
USC Southbank
🇦🇺Brisbane, Queensland, Australia
Emeritus Research Melbourne
🇦🇺Melbourne, Victoria, Australia
The Peter Doherty Institute for Infection and Immunity
🇦🇺Melbourne, Victoria, Australia
Tropical Disease Foundation - Putatan Health Center
🇵🇭Muntinlupa City, Philippines
Sutherland Shire Clinical Research - Walski
🇦🇺Miranda, New South Wales, Australia
Paratus Clinical Blacktown
🇦🇺Sydney, New South Wales, Australia
Griffith University Clinical Trials Unit
🇦🇺Sydney, New South Wales, Australia
Nucleus Network Brisbane (Q-Pharm)
🇦🇺Brisbane, Queensland, Australia
Paratus Clinical Brisbane
🇦🇺Brisbane, Queensland, Australia
Austrials -Sunshine
🇦🇺Melbourne, Victoria, Australia
USC Sippy Down
🇦🇺Sunshine Coast, Queensland, Australia
Nucleus Network
🇦🇺Melbourne, Victoria, Australia
Veritus Research
🇦🇺Melbourne, Victoria, Australia
Clinitrials - Mount Site
🇦🇺Perth, Western Australia, Australia
Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)
🇭🇳San Pedro Sula, Honduras
Far Eastern University - Nicanor R. M Foundation
🇵🇭Quezon City, Philippines
CMAX
🇦🇺Adelaide, South Australia, Australia
Wollongong Clinical Research
🇦🇺Wollongong, New South Wales, Australia
Austrials - St. Leonards
🇦🇺Sydney, New South Wales, Australia
IICIMED
🇨🇷San Jose, Costa Rica
Paratus Clinical Canberra
🇦🇺Canberra, Australian Capital Territory, Australia
Clínica San Agustín
🇨🇷San José, Costa Rica
Organización y centro de investigación clínica Ochoa (OCINCO)
🇭🇳Comayagua, Honduras
Inversiones en Investigación Médica S.A (INVERIME)
🇭🇳Tegucigalpa, Honduras