COVID-19Phase 3NCT06279871
Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults
A Phase 3 study testing ARCT-2303, Influenza vaccine and Influenza vaccine, adjuvanted in people with COVID-19, run by Arcturus Therapeutics, Inc. at 29 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19
- What is being tested?
- ARCT-2303, Influenza vaccine and Influenza vaccine, adjuvanted
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,514 participants
- Where
- 29 sitesin 4 countries
- Study dates
- 27 Mar 2024to 21 Nov 2024
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
29 sites in 4 countries.
29 sites in 4 countries
Australia22 sites
CMAX
Adelaide, South Australia
Nucleus Network Brisbane (Q-Pharm)
Brisbane, Queensland
Paratus Clinical Brisbane
Brisbane, Queensland
USC Southbank
Brisbane, Queensland
Paratus Clinical Canberra
Canberra, Australian Capital Territory
Paratus Clinical Central Coast
Central Coast, New South Wales
Austrials -Sunshine
Melbourne, Victoria
Emeritus Research Melbourne
Melbourne, Victoria
Nucleus Network
Melbourne, Victoria
The Peter Doherty Institute for Infection and Immunity
Melbourne, Victoria
Veritus Research
Melbourne, Victoria
Sutherland Shire Clinical Research - Walski
Miranda, New South Wales
USC Morayfield
Morayfield, Queensland
Clinitrials - Mount Site
Perth, Western Australia
USC Sippy Down
Sunshine Coast, Queensland
Australian Clinical Research Network (ACRN)
Sydney, New South Wales
Austrials - St. Leonards
Sydney, New South Wales
Emeritus Research Sydney
Sydney, New South Wales
Griffith University Clinical Trials Unit
Sydney, New South Wales
Northern Beaches Clinical Research - Walski
Sydney, New South Wales
Paratus Clinical Blacktown
Sydney, New South Wales
Wollongong Clinical Research
Wollongong, New South Wales
Honduras3 sites
Organización y centro de investigación clínica Ochoa (OCINCO)
Comayagua
Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)
San Pedro Sula
Inversiones en Investigación Médica S.A (INVERIME)
Tegucigalpa
Philippines2 sites
Tropical Disease Foundation - Putatan Health Center
City of Muntinlupa
Far Eastern University - Nicanor R. M Foundation
Quezon City
About this study
Official title: A Phase 3, Multicenter, Observer-blind, Randomized, Controlled Study to Evaluate the Immunogenicity, Reactogenicity, and Safety of a Self-Amplifying RNA COVID-19 Vaccine (ARCT-2303), Administered Concomitantly With Quadrivalent Influenza Vaccines, in Adults
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- ARCT-2303, Influenza vaccine, Influenza vaccine, adjuvanted, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARCT-2303Biological
Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)
Influenza vaccineBiological
Licensed cell-based influenza vaccine
Influenza vaccine, adjuvantedBiological
Licensed influenza vaccine, adjuvanted
PlaceboOther
0.9% saline
| Study group | Role | What they receive |
|---|---|---|
| Group 1a (ARCT-2303/Influenza vaccine) | Experimental | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine; Other: Placebo |
| Group 2a (ARCT-2303) | Experimental | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine; Other: Placebo |
| Group 3a (Influenza vaccine) | Active comparator | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine; Other: Placebo |
| Group 1b (ARCT-2303/ Influenza vaccine) | Experimental | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine, adjuvanted; Other: Placebo |
| Group 2b (ARCT-2303) | Experimental | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine, adjuvanted; Other: Placebo |
| Group 3b (Influenza vaccine) | Active comparator | 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. Receives: Biological: ARCT-2303; Biological: Influenza vaccine, adjuvanted; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: Day 29
Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29
Measured: Day 29
Secondary outcomes (19)
Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181
Measured: 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.
Measured: 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
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 up to Day 181
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start27 Mar 2024
- Primary completion9 Oct 2024
- Study completion21 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,514 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arcturus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Seqirus, Novotech (Australia) Pty Limited
- Responsible party
- Sponsor
- Investigators
- Clinical Program Director, Study director, Arcturus Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06279871
- Sponsor's protocol ID
- ARCT-2303-01
- Status last verified
- Nov 2025
- First submitted
- 23 Feb 2024
- Last updated
- 12 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Giles ML, Tabora C, Baccarini C, Barrientos L, Vargas JC, Montellano ME, Nguyen P, Deshmukh S, Neville M, Hohenboken M, van Boxmeer J, Jin H, Bugarini R, Liu X, Walson JL, Verhoeven C, Smolenov I. Immunogenicity and safety of self-amplifying mRNA COVID-19 vaccine (ARCT-2303), with or without co-administration of seasonal inactivated influenza vaccine in adults: a phase 3, randomised, controlled, observer-blind, multicentre study. EClinicalMedicine. 2025 Aug 20;87:103428. doi: 10.1016/j.eclinm.2025.103428. eCollection 2025 Sep.
PubMed 40896462