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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06279871
• Other study ID #: ARCT-2303-01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 27, 2024
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Arcturus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 authorized COVID-19 vaccine.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1680
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• ARCT-2303
Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5)
• Influenza vaccine
Licensed cell-based influenza vaccine
• Influenza vaccine, adjuvanted
Licensed influenza vaccine, adjuvanted

Other:
• Placebo
0.9% saline

Locations

Country	Name	City	State
Australia	CMAX	Adelaide	South Australia
Australia	Nucleus Network Brisbane (Q-Pharm)	Brisbane	Queensland
Australia	Paratus Clinical Brisbane	Brisbane	Queensland
Australia	USC Southbank	Brisbane	Queensland
Australia	Paratus Clinical Canberra	Canberra	Australian Capital Territory
Australia	Paratus Clinical Central Coast	Central Coast	New South Wales
Australia	Austrials -Sunshine	Melbourne	Victoria
Australia	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	Sutherland Shire Clinical Research - Walski	Miranda	New South Wales
Australia	USC Morayfield	Morayfield	Queensland
Australia	Clinitrials - Mount Site	Perth	Western Australia
Australia	USC Sippy Down	Sunshine Coast	Queensland
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
Costa Rica	IICIMED	San Jose
Costa Rica	Clínica San Agustín	San José
Honduras	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
Philippines	Tropical Disease Foundation - Putatan Health Center	Muntinlupa City
Philippines	Far Eastern University - Nicanor R. M Foundation	Quezon City

Sponsors (3)

Lead Sponsor	Collaborator
Arcturus Therapeutics, Inc.	Novotech (Australia) Pty Limited, Seqirus

Countries where clinical trial is conducted

Australia,  Costa Rica,  Honduras,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SARS-CoV-2 neutralizing antibody titers	Immune response as measured by geometric mean titers (GMTs) of neutralizing antibodies against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)	Day 29
Primary	SARS-CoV-2 neutralizing antibody seroconversion rates	Immune response as measured by SARS-CoV-2 neutralizing antibody seroconversion rates against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)	Day 29
Primary	Hemagglutination Inhibition (HI) titers	Immune response as measured by GMTs against influenza vaccine strains (Group 1a; Group 3a)	Day 1, Day 29
Primary	SARS-CoV-2 neutralizing antibody titers	Immune response as measured by GMTs of neutralizing antibodies against Omicron XBB.1.5 subvariant (Group 1a; Group 2a)	Day 29
Secondary	SARS-CoV-2 neutralizing antibody titers	GMTs of SARS-CoV-2 neutralizing antibody titers against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)	Day 29
Secondary	SARS-CoV-2 neutralizing antibody seroconversion rates	SARS-CoV-2 neutralizing antibody seroconversion rates against Omicron XBB.1.5 subvariant (Groups 2a and 2b; a comparator group from a previous study)	Day 29
Secondary	SARS-CoV-2 neutralizing antibody response (Group 1a; Group 2a)	SARS-CoV-2 neutralizing antibody responses against Omicron XBB.1.5 subvariant as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with antibody titer = lower limit of quantitation (LLOQ) (Group 1a; Group 2a)	Days 1, 29 and 181
Secondary	Hemagglutination Inhibition (HI) titers	HI assay titers against influenza vaccine strains as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with HI titers =1:40 (Group 1a; Group 3a)	Day 1, Day 29
Secondary	SARS-CoV-2 neutralizing antibody responses	SARS-CoV-2 neutralizing antibody responses against Omicron XBB.1.5 subvariant as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with antibody titer = LLOQ (Group 1b; Group 2b)	Day 181
Secondary	Hemagglutination Inhibition (HI) assay titers	HI assay titers against influenza vaccine strains as measured by GMT, Geometric Mean Fold Rise (post/pre-vaccination), proportion of participants with seroconversion and proportion of participants with HI titers =1:40 (Group 1b; Group 3b)	Day 29
Secondary	Local and systemic adverse events (AEs)	Proportion of participants with local and systemic solicited AEs	Day 1 to Day 8 after each vaccination
Secondary	Unsolicited AEs	Proportion of participants with unsolicited AEs	Day 1 to Day 29 after each vaccination
Secondary	SAE, Medically Attended Adverse Events (MAAE), Adverse Events of Special Interest (AESI), and AE leading to early termination	Proportion of participants with SAE/MAAE/AESI/AE leading to early termination from study	Day 1 to Day 181