This is a multicenter, observer-blind, randomized, controlled phase 3 study to evaluatethe immunogenicity, reactogenicity, and safety of an investigational self-amplifying RNACOVID-19 vaccine (ARCT-2303) administered concomitantly with quadrivalent influenzavaccines 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.
Biological: ARCT-2303
Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)
Biological: Influenza vaccine
Licensed cell-based influenza vaccine
Biological: Influenza vaccine, adjuvanted
Licensed influenza vaccine, adjuvanted
Other: Placebo
0.9% saline
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.
Paratus Clinical Canberra
Canberra 2172517, Australian Capital Territory 2177478, Australia
Paratus Clinical Central Coast
Central Coast 8310663, New South Wales 2155400, Australia
Sutherland Shire Clinical Research - Walski
Miranda 2157495, New South Wales 2155400, Australia
Australian Clinical Research Network (ACRN)
Sydney 2147714, New South Wales 2155400, Australia
Austrials - St. Leonards
Sydney 2147714, New South Wales 2155400, Australia
Emeritus Research Sydney
Sydney 2147714, New South Wales 2155400, Australia
Griffith University Clinical Trials Unit
Sydney 2147714, New South Wales 2155400, Australia
Northern Beaches Clinical Research - Walski
Sydney 2147714, New South Wales 2155400, Australia
Paratus Clinical Blacktown
Sydney 2147714, New South Wales 2155400, Australia
Wollongong Clinical Research
Wollongong 2171507, New South Wales 2155400, Australia
Nucleus Network Brisbane Clinic
Brisbane 2174003, Queensland 2152274, Australia
Paratus Clinical Brisbane
Brisbane 2174003, Queensland 2152274, Australia
USC Southbank
Brisbane 2174003, Queensland 2152274, Australia
USC Morayfield
Morayfield 2156934, Queensland 2152274, Australia
USC Sippy Down
Sunshine Coast 10630449, Queensland 2152274, Australia
CMAX Clinical Research
Adelaide 2078025, South Australia 2061327, Australia
Austrials -Sunshine
Melbourne 2158177, Victoria 2145234, Australia
Emeritus Research Melbourne
Melbourne 2158177, Victoria 2145234, Australia
Nucleus Network - Melbourne Clinic
Melbourne 2158177, Victoria 2145234, Australia
The Peter Doherty Institute for Infection and Immunity
Melbourne 2158177, Victoria 2145234, Australia
Veritus Research
Melbourne 2158177, Victoria 2145234, Australia
Clinitrials - Mount Site
Perth 2063523, Western Australia 2058645, Australia
Clínica San Agustín
San José 3621849, Costa Rica
IICIMED
San José 3621849, Costa Rica
Organización y centro de investigación clínica Ochoa (OCINCO)
Comayagua 3613321, Honduras
Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)
San Pedro Sula 3601782, Honduras
Inversiones en Investigación Médica S.A (INVERIME)
Tegucigalpa 3600949, Honduras
Tropical Disease Foundation - Putatan Health Center
City of Muntinlupa 1699076, Philippines
Far Eastern University - Nicanor R. M Foundation
Quezon City 1692192, Philippines
Clinical Program Director, Study Director
Arcturus Therapeutics