Safety and Immunogenicity Study of Self-Amplifying RNA Pandemic Influenza Vaccine in Adults

March 30, 2026 updated by: Arcturus Therapeutics, Inc.

A Phase 1, First-in-human, Randomized, Observer-blind, Parallel Design, Controlled, Dose Level and Schedule-finding Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Self-Amplifying mRNA Pandemic Influenza Vaccine (ARCT-2304) When Administered to Healthy Adults

The goal of this clinical trial is to evaluate the safety and immune responses of three different dose levels a self-amplifying RNA pandemic influenza vaccine (ARCT-2304) in adults. The key objectives of the study are:

  • To evaluate safety and reactogenicity of different dose levels of the ARCT-2304 vaccine
  • To describe the Immune responses of different dose levels of the ARCT-2304 vaccine as measured by hemagglutination inhibition (HAI) and neuraminidase enzyme-linked lectin (ELLA) antibody responses

Researchers will compare the results with licensed influenza vaccines to select the most optimal dose level and schedule for vaccine administration in terms of safety and immunogenicity for further development of the vaccine.

Participants will receive 2 doses of the ARCT-2304 vaccine or 1 dose of licensed influenza vaccine and 1 dose of placebo.

They will be asked:

  • to complete a daily diary for 7 days after each vaccination, answering questions how they have been feeling on that day.
  • to provide blood samples at each visit in the clinic
  • to comply with all study visits and procedures (e.g., be available for planned telephone contacts and unscheduled clinic visits, if required)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Phase 1, first-in-human, randomized, controlled, observer blind, dose level and schedule-finding study, to evaluate the safety, reactogenicity, and immunogenicity of a self-amplifying mRNA pandemic influenza (H5N1) vaccine (ARCT-2304) when administered as a 2-dose vaccination series to healthy adults in comparison with an inactivated influenza vaccine.

Study drug (ARCT-2304 or control) will be administered as a 2-dose vaccination series as an intramuscular (IM) injection. The study comprises two parts.

In Part 1, 120 participants (young adults) will be randomized to one of the three dose levels of the ARCT-2304 vaccine or control vaccine. Participants will be further randomized to one of the two different vaccination schedules.

In Part 2, 80 participants (older adults) will be randomized to one of the three dose levels of the ARCT-2304 vaccine or control vaccine. Participants will be further randomized to one of the two different vaccination schedules.

Investigational Vaccine: ARCT-2304

Control Vaccines: licensed influenza vaccines

Study Type

Interventional

Enrollment (Actual)

212

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Mesa, California, United States, 91942
        • Velocity Clinical Research
      • San Bernardino, California, United States, 92408
        • Velocity Clinical Research
    • Colorado
      • Longmont, Colorado, United States, 80501
        • Tekton Research
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • CTI Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Main Inclusion Criteria:

  • Individuals are male or female adults 18-80 years of age.
  • Healthy participants or participants with pre-existing stable medical conditions.
  • Individuals of childbearing potential must be willing to adhere to contraceptive requirements.

Main Exclusion Criteria:

  • Individuals with acute medical conditions or febrile illness, including body temperature ≥100.4°F (≥38.0°C measured by any method) within 3 days prior to randomization.
  • Individuals with a known history of severe hypersensitivity reactions, including anaphylaxis, or other significant adverse reactions to any mRNA vaccine, influenza vaccine, or excipients.
  • Individuals with a history of myocarditis, pericarditis, myopericarditis, or cardiomyopathy.
  • Individuals who received any influenza vaccine within 3 months prior to first vaccine administration or plan to receive an influenza vaccine during the study period.
  • Individuals who have received mRNA vaccination within 60 days before the first vaccine administration.
  • Individuals who have received or plan to receive an A/H5N1 influenza vaccine and/or individuals who had substantial exposure to or direct contact with poultry, wild birds, live cattle, or raw milk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dose of ARCT-2304, Schedule 1, Young Adults

Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: Mid dose of ARCT-2304, Schedule 1, Young Adults

Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: High dose of ARCT-2304, Schedule 1, Young Adults

High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Active Comparator: Control, Schedule 1, Young Adults

Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Other: Placebo Vaccine
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • saline
Biological: Control vaccine (licensed seasonal influenza vaccine) younger adults
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Influenza vaccine
Experimental: Low dose of ARCT-2304, Schedule 1, Older Adults

Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: Mid dose of ARCT-2304, Schedule 1, Older Adults

Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: High dose of ARCT-2304, Schedule 1, Older Adults

High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Active Comparator: Control, Schedule 1, Older Adults

Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine older adult and saline
Other: Placebo Vaccine
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • saline
Biological: Control vaccine (licensed seasonal influenza vaccine) older adults
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Influenza vaccine
Experimental: Low dose of ARCT-2304, Schedule 2, Young Adults

Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: Mid dose of ARCT-2304, Schedule 2, Young Adults

Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: High dose of ARCT-2304, Schedule 2, Young Adults

High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Active Comparator: Control, Schedule 2, Young Adults

Young Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Other: Placebo Vaccine
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • saline
Biological: Control vaccine (licensed seasonal influenza vaccine) younger adults
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Influenza vaccine
Experimental: Low dose of ARCT-2304, Schedule 2, Older Adults

Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: Mid dose of ARCT-2304, Schedule 2, Older Adults

Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Experimental: High dose of ARCT-2304, Schedule 2, Older Adults

High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Biological: ARCT-2304
Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Self-Amplifying mRNA pandemic Influenza vaccine
Active Comparator: Control, Schedule 2, Older Adults

Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle.

Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine older adult and saline placebo vaccine
Other: Placebo Vaccine
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • saline
Biological: Control vaccine (licensed seasonal influenza vaccine) older adults
Each participant will receive one intramuscular (IM) dose into the deltoid muscle.
Other Names:
  • Influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants reporting local Adverse Events
Time Frame: For 7 days following each study vaccination
Solicited local AEs including injection site pain, erythema, and swelling
For 7 days following each study vaccination
Percentage of participants reporting systemic Adverse Events
Time Frame: For 7 days following each study vaccination
Solicited systemic AEs including fatigue, headache, myalgia, arthralgia, nausea, dizziness, chills, and fever
For 7 days following each study vaccination
Percentage of participants reporting unsolicited Adverse Events
Time Frame: For 28 days following each study vaccination
Spontaneously reported adverse events and as elicited by investigational site staff
For 28 days following each study vaccination
Percentage of participants reporting laboratory or vital signs abnormalities
Time Frame: For 28 days following each study vaccination
Abnormal clinically significant values
For 28 days following each study vaccination
Percentage of participants reporting serious adverse events, medically attended adverse events, adverse events of special interest, and adverse events leading to early termination
Time Frame: For 28 days following each study vaccination
Spontaneously reported adverse events and as elicited by investigational site staff
For 28 days following each study vaccination
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein
Time Frame: For 28 days following study second vaccination
HAI antibody levels expressed as GMT, GMFRs, SCRs, and HAI titers
For 28 days following study second vaccination
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins
Time Frame: For 28 days following study second vaccination
ELLA antibody levels expressed as GMT, GMFRs, SCRs, and HAI titers
For 28 days following study second vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants reporting serious adverse events, medically attended adverse events, adverse events of special interest, and adverse events leading to early termination
Time Frame: For 240 days following study vaccination
Spontaneously reported adverse events and as elicited by investigational site staff
For 240 days following study vaccination
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein
Time Frame: For 240 days following study vaccination
HAI antibody levels expressed as GMT, GMFRs, SCRs and HAI titers
For 240 days following study vaccination
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins
Time Frame: For 240 days following study vaccination
ELLA antibody levels expressed as GMT, GMFRs, SCRs and HAI titers
For 240 days following study vaccination
Serum neutralizing (MN) antibody levels against the HA glycoprotein
Time Frame: For 28 days following study second vaccination
MN antibody levels expressed as GMT, GMFRs, SCRs, and MN titers
For 28 days following study second vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arcturus Therapeutics, Inc.

Collaborators

Biomedical Advanced Research and Development Authority

Investigators

  • Study Director: Clinical Program Director, Arcturus Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2024

Primary Completion (Actual)

June 13, 2025

Study Completion (Actual)

December 5, 2025

Study Registration Dates

First Submitted

September 16, 2024

First Submitted That Met QC Criteria

September 17, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARCT-2304-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will only be made available to study investigators at this time.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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