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

NCT06279871 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ARCT-2303-01
• Study Type: interventional
• Target: 1,514
• Locations: 4 countries
• Sites: 29

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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.

  Day 29

• Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29

  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

  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

  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

  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

  Days 1 and 29

• Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29

  Days 1 and 29

Study Arms (6)

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.

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.

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.

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.

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.

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.

Biological: ARCT-2303; Biological: Influenza vaccine, adjuvanted; Other: Placebo

Interventions

ARCT-2303 BIOLOGICAL

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

Group 1a (ARCT-2303/Influenza vaccine); Group 1b (ARCT-2303/ Influenza vaccine); Group 2a (ARCT-2303); Group 2b (ARCT-2303); Group 3a (Influenza vaccine); Group 3b (Influenza vaccine)

Influenza vaccine BIOLOGICAL

Licensed cell-based influenza vaccine

Group 1a (ARCT-2303/Influenza vaccine); Group 2a (ARCT-2303); Group 3a (Influenza vaccine)

Influenza vaccine, adjuvanted BIOLOGICAL

Licensed influenza vaccine, adjuvanted

Group 1b (ARCT-2303/ Influenza vaccine); Group 2b (ARCT-2303); Group 3b (Influenza vaccine)

Placebo OTHER

0.9% saline

Group 1a (ARCT-2303/Influenza vaccine); Group 1b (ARCT-2303/ Influenza vaccine); Group 2a (ARCT-2303); Group 2b (ARCT-2303); Group 3a (Influenza vaccine); Group 3b (Influenza vaccine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• , Individuals are male, female, or transgender adults ≥18 years of age.
• \. Healthy participants or participants with pre-existing stable medical conditions.
• \. Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
• \. Individuals must have been previously vaccinated with COVID-19 vaccines.
• \. Individuals of childbearing potential must be willing to adhere to contraceptive requirements.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arcturus Therapeutics, Inc.: lead
• Seqirus: collaborator
• Novotech (Australia) Pty Limited: collaborator

Study Sites (29)

Paratus Clinical Canberra

Canberra, Australian Capital Territory, Australia

Location

Paratus Clinical Central Coast

Central Coast, New South Wales, Australia

Location

Sutherland Shire Clinical Research - Walski

Miranda, New South Wales, Australia

Location

Australian Clinical Research Network (ACRN)

Sydney, New South Wales, Australia

Location

Austrials - St. Leonards

Sydney, New South Wales, Australia

Location

Emeritus Research Sydney

Sydney, New South Wales, Australia

Location

Griffith University Clinical Trials Unit

Sydney, New South Wales, Australia

Location

Northern Beaches Clinical Research - Walski

Sydney, New South Wales, Australia

Location

Paratus Clinical Blacktown

Sydney, New South Wales, Australia

Location

Wollongong Clinical Research

Wollongong, New South Wales, Australia

Location

Nucleus Network Brisbane (Q-Pharm)

Brisbane, Queensland, Australia

Location

Paratus Clinical Brisbane

Brisbane, Queensland, Australia

Location

USC Southbank

Brisbane, Queensland, Australia

Location

USC Morayfield

Morayfield, Queensland, Australia

Location

USC Sippy Down

Sunshine Coast, Queensland, Australia

Location

CMAX

Adelaide, South Australia, Australia

Location

Austrials -Sunshine

Melbourne, Victoria, Australia

Location

Emeritus Research Melbourne

Melbourne, Victoria, Australia

Location

Nucleus Network

Melbourne, Victoria, Australia

Location

The Peter Doherty Institute for Infection and Immunity

Melbourne, Victoria, Australia

Location

Veritus Research

Melbourne, Victoria, Australia

Location

Clinitrials - Mount Site

Perth, Western Australia, Australia

Location

Clínica San Agustín

San José, Costa Rica

Location

IICIMED

San José, Costa Rica

Location

Organización y centro de investigación clínica Ochoa (OCINCO)

Comayagua, Honduras

Location

Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)

San Pedro Sula, Honduras

Location

Inversiones en Investigación Médica S.A (INVERIME)

Tegucigalpa, Honduras

Location

Tropical Disease Foundation - Putatan Health Center

City of Muntinlupa, Philippines

Location

Far Eastern University - Nicanor R. M Foundation

Quezon City, Philippines

Location

Related Publications (1)

• 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.

  PMID: 40896462 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Arcturus Therapeutics, Inc.
• Organization: Arcturus Therapeutics, Inc.

clinicaltrials@arcturusrx.com

858-900-2660

Study Officials

• Clinical Program Director

  Arcturus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: February 28, 2024
• Study Start: March 27, 2024
• Primary Completion: October 9, 2024
• Study Completion: November 21, 2024
• Last Updated: December 12, 2025
• Results First Posted: December 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CO (2); AU (22); HO (3); PH (2)