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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: ARCT-2303; Biological: Influenza vaccine; Other: Placebo; Biological: Influenza vaccine, adjuvanted

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.

• Study Type: Interventional
• Enrollment (Estimated): 1680
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure Manager; Phone Number: (858) 900-2660; Email: clinicaltrials@arcturusrx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Biological: Influenza vaccine; Licensed cell-based influenza vaccine; Other: Placebo; 0.9% saline
Experimental: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Biological: Influenza vaccine; Licensed cell-based influenza vaccine; Other: Placebo; 0.9% saline
Active Comparator: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Biological: Influenza vaccine; Licensed cell-based influenza vaccine; Other: Placebo; 0.9% saline
Experimental: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Other: Placebo; 0.9% saline; Biological: Influenza vaccine, adjuvanted; Licensed influenza vaccine, adjuvanted
Experimental: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Other: Placebo; 0.9% saline; Biological: Influenza vaccine, adjuvanted; Licensed influenza vaccine, adjuvanted
Active Comparator: 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.	Biological: ARCT-2303; Self-Amplifying RNA COVID-19 vaccine (Omicron XBB.1.5); Other: Placebo; 0.9% saline; Biological: Influenza vaccine, adjuvanted; Licensed influenza vaccine, adjuvanted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Hemagglutination Inhibition (HI) titers	Immune response as measured by GMTs against influenza vaccine strains (Group 1a; Group 3a)	Day 1, Day 29
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Local and systemic adverse events (AEs)	Proportion of participants with local and systemic solicited AEs	Day 1 to Day 8 after each vaccination
Unsolicited AEs	Proportion of participants with unsolicited AEs	Day 1 to Day 29 after each vaccination
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

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.
• Collaborators: Novotech (Australia) Pty Limited; Seqirus
• Investigators: Study Director: Clinical Program Director, Arcturus Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 23, 2024
• First Submitted That Met QC Criteria: February 23, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: ARCT-2303-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No