Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults

NCT ID: NCT06279871

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1514 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-27
• Study Completion Date: 2024-11-21

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1a (ARCT-2303/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 Type: EXPERIMENTAL

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine

Intervention Type: BIOLOGICAL

Licensed cell-based influenza vaccine

Placebo

Intervention Type: OTHER

0.9% saline

Group 2a (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 Type: EXPERIMENTAL

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine

Intervention Type: BIOLOGICAL

Licensed cell-based influenza vaccine

Placebo

Intervention Type: OTHER

0.9% saline

Group 3a (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 Type: ACTIVE_COMPARATOR

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine

Intervention Type: BIOLOGICAL

Licensed cell-based influenza vaccine

Placebo

Intervention Type: OTHER

0.9% saline

Group 1b (ARCT-2303/ Influenza vaccine)

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 Type: EXPERIMENTAL

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine, adjuvanted

Intervention Type: BIOLOGICAL

Licensed influenza vaccine, adjuvanted

Placebo

Intervention Type: OTHER

0.9% saline

Group 2b (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 Type: EXPERIMENTAL

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine, adjuvanted

Intervention Type: BIOLOGICAL

Licensed influenza vaccine, adjuvanted

Placebo

Intervention Type: OTHER

0.9% saline

Group 3b (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 Type: ACTIVE_COMPARATOR

ARCT-2303

Intervention Type: BIOLOGICAL

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Influenza vaccine, adjuvanted

Intervention Type: BIOLOGICAL

Licensed influenza vaccine, adjuvanted

Placebo

Intervention Type: OTHER

0.9% saline

Interventions

ARCT-2303

Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)

Intervention Type: BIOLOGICAL

Influenza vaccine

Licensed cell-based influenza vaccine

Intervention Type: BIOLOGICAL

Influenza vaccine, adjuvanted

Licensed influenza vaccine, adjuvanted

Intervention Type: BIOLOGICAL

Placebo

0.9% saline

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seqirus

INDUSTRY

Sponsor Role: collaborator

Novotech (Australia) Pty Limited

INDUSTRY

Sponsor Role: collaborator

Arcturus Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Program Director

Role: STUDY_DIRECTOR

Arcturus Therapeutics

Locations

Emeritus Research Melbourne

Melbourne, Victoria, Australia

Nucleus Network

Melbourne, Victoria, Australia

The Peter Doherty Institute for Infection and Immunity

Melbourne, Victoria, Australia

Veritus Research

Melbourne, Victoria, Australia

Clinitrials - Mount Site

Perth, Western Australia, Australia

Clínica San Agustín

San José, , Costa Rica

IICIMED

San José, , Costa Rica

Organización y centro de investigación clínica Ochoa (OCINCO)

Comayagua, , Honduras

Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)

San Pedro Sula, , Honduras

Inversiones en Investigación Médica S.A (INVERIME)

Tegucigalpa, , Honduras

Tropical Disease Foundation - Putatan Health Center

City of Muntinlupa, , Philippines

Far Eastern University - Nicanor R. M Foundation

Quezon City, , Philippines

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

Nucleus Network Brisbane (Q-Pharm)

Brisbane, Queensland, Australia

Paratus Clinical Brisbane

Brisbane, Queensland, Australia

USC Southbank

Brisbane, Queensland, Australia

USC Morayfield

Morayfield, Queensland, Australia

USC Sippy Down

Sunshine Coast, Queensland, Australia

CMAX

Adelaide, South Australia, Australia

Austrials -Sunshine

Melbourne, Victoria, Australia

Countries

Australia; Costa Rica; Honduras; Philippines

References

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.

Reference Type: DERIVED

PMID: 40896462 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ARCT-2303-01

Identifier Type: -

Identifier Source: org_study_id