Clinical trial NCT06279871: Immunogenicity and Safety Study of Self-amplifying MRNA COVID-19 Vaccine Administered with Influenza Vaccines in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Arcturus Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Seqirus
name: Novotech (Australia) Pty Limited
First posted: 2024-02-28
Enrollment: 1499
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: SARS-CoV-2 neutralizing antibody titers
timeFrame: Day 29
measure: SARS-CoV-2 neutralizing antibody seroconversion rates
timeFrame: Day 29
measure: Hemagglutination Inhibition (HI) titers
timeFrame: Day 1, Day 29
measure: SARS-CoV-2 neutralizing antibody titers
timeFrame: Day 29
Secondary outcomes:
measure: SARS-CoV-2 neutralizing antibody titers
timeFrame: Day 29
measure: SARS-CoV-2 neutralizing antibody seroconversion rates
timeFrame: Day 29
measure: SARS-CoV-2 neutralizing antibody response (Group 1a; Group 2a)
timeFrame: Days 1, 29 and 181
measure: Hemagglutination Inhibition (HI) titers
timeFrame: Day 1, Day 29
measure: SARS-CoV-2 neutralizing antibody responses
timeFrame: Day 181
measure: Hemagglutination Inhibition (HI) assay titers
timeFrame: Day 29
measure: Local and systemic adverse events (AEs)
timeFrame: Day 1 to Day 8 after each vaccination
measure: Unsolicited AEs
timeFrame: Day 1 to Day 29 after each vaccination
measure: SAE, Medically Attended Adverse Events (MAAE), Adverse Events of Special Interest (AESI), and AE leading to early termination
timeFrame: Day 1 to Day 181
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: Paratus Clinical Canberra
state: Australian Capital Territory
city: Central Coast
country: Australia
facility: Paratus Clinical Central Coast
state: New South Wales
city: Miranda
country: Australia
facility: Sutherland Shire Clinical Research - Walski
state: New South Wales
city: Sydney
country: Australia
facility: Australian Clinical Research Network (ACRN)
state: New South Wales
city: Sydney
country: Australia
facility: Austrials - St. Leonards
state: New South Wales
city: Sydney
country: Australia
facility: Emeritus Research Sydney
state: New South Wales
city: Sydney
country: Australia
facility: Griffith University Clinical Trials Unit
state: New South Wales
city: Sydney
country: Australia
facility: Northern Beaches Clinical Research - Walski
state: New South Wales
city: Sydney
country: Australia
facility: Paratus Clinical Blacktown
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Clinical Research
state: New South Wales
city: Brisbane
country: Australia
facility: Nucleus Network Brisbane (Q-Pharm)
state: Queensland
city: Brisbane
country: Australia
facility: Paratus Clinical Brisbane
state: Queensland
city: Brisbane
country: Australia
facility: USC Southbank
state: Queensland
city: Morayfield
country: Australia
facility: USC Morayfield
state: Queensland
city: Sunshine Coast
country: Australia
facility: USC Sippy Down
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
city: Melbourne
country: Australia
facility: Austrials -Sunshine
state: Victoria
city: Melbourne
country: Australia
facility: Emeritus Research Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
city: Melbourne
country: Australia
facility: The Peter Doherty Institute for Infection and Immunity
state: Victoria
city: Melbourne
country: Australia
facility: Veritus Research
state: Victoria
city: Perth
country: Australia
facility: Clinitrials - Mount Site
state: Western Australia
city: San Jose
country: Costa Rica
facility: IICIMED
city: San José
country: Costa Rica
facility: Clínica San Agustín
city: Comayagua
country: Honduras
facility: Organización y centro de investigación clínica Ochoa (OCINCO)
city: San Pedro Sula
country: Honduras
facility: Deposito de Medicamentos de Investigación Cousin Agustín (DEMEDICA)
city: Tegucigalpa
country: Honduras
facility: Inversiones en Investigación Médica S.A (INVERIME)
city: Muntinlupa City
country: Philippines
facility: Tropical Disease Foundation - Putatan Health Center
city: Quezon City
country: Philippines
facility: Far Eastern University - Nicanor R. M Foundation
Study officials:
affiliation: Arcturus Therapeutics
name: Clinical Program Director
role: STUDY_DIRECTOR
References: