Safety and Immunogenicity First-in-human Dose-ranging Study of Self-Amplifying RNA Seasonal Influenza Vaccine in Adults

A Phase 1, First-in-Human, Randomized, Observer-blind, Controlled, Dose-ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Self-Amplifying mRNA Seasonal Influenza Vaccine (ARCT-2138), When Administered to Healthy Adults

This is a safety and Immunogenicity first-in-human dose-ranging study of self-amplifying RNA Seasonal Influenza Vaccine (ARCT-2138) in adults.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: ARCT-2138; Biological: Licensed Quadrivalent Vaccine for younger adults; Biological: Licensed Quadrivalent Vaccine for older adults

Detailed Description

Phase 1, first-in-human, randomized, controlled, observer blind (open label Part 4 only), dose-escalation study, to assess the safety, tolerability, and immunogenicity of different dose levels of the ARCT-2138 vaccine, administered as a single dose to healthy young and older adults, in comparison with an inactivated influenza vaccine.

Study drug (ARCT-2138 or control) will be administered as an intramuscular (IM) injection. The study comprises of four parts. In Part 1, escalating dose levels of ARCT-2138 given as a single injection to younger adults will be evaluated sequentially.

Low, medium, and high dose levels of ARCT-2138 (as recommended by DSMB) will be further evaluated in younger adults in Part 2. Part 3 will evaluate low, medium, and high dose levels of ARCT-2138 (as recommended by DSMB) in older adults.

Part 4 (dose expansion phase) will administer a lower dose of ARCT-2138 in young adults.

Investigational Vaccine: ARCT-2138 (Part 1-3 only, no control vaccine for Part 4) Control Vaccines: licensed influenza vaccines (inactivated)

• For younger adults: Flucelvax® Quad, Seqirus Pty Ltd.
• For older adults: Fluad® Quad, Seqirus Pty Ltd.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Nucleus Network Brisbane Clinic
  • Victoria
    • Melbourne, Victoria, Australia, 3124
      • Emeritus Research Camberwell

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 to 49 years of age or 65 to 85 years of age.
2. Healthy participants or participants with pre-existing stable medical conditions. Pre-existing stable medical condition means a subject who: has full capacity of daily activity and no major medication modification; has not undergone surgical or minimally invasive intervention or had any hospitalization/emergency room visit for the specific medical condition within 3 months prior to Day 1.
3. Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
4. Individuals who have not received influenza vaccine within 6 months prior to enrollment.
5. Individuals must agree to comply with all study visits and procedures (including blood tests, nasopharyngeal swabs, diary completion, receipt of telephone calls from the site, willingness to be available for Unscheduled Clinic Visits).
6. Individuals of childbearing potential must be willing to adhere to contraceptive requirements.

Exclusion Criteria:

1. Individuals with acute medical illness or febrile illness, including body temperature >100.4°F (>38.0°C) within 3 days prior to Randomization. These individuals may be offered the opportunity to enter the study after fever and illness has stabilized. Participants with suspected or confirmed influenza should be excluded and referred for medical care. Rescreening will be permitted for individuals who are presented with suspected influenza if another diagnosis is confirmed.
2. Individuals with any medical, neurological, or psychiatric condition that, in the opinion of the investigator, could place the participant at an unacceptable risk of injury or render the participant unable to comply with all study procedures and achieve successful completion of the trial.
3. Individuals with a known history of severe hypersensitivity reactions, including anaphylaxis, or other significant adverse reactions to any mRNA vaccine, influenza vaccine, or excipients.
4. Individuals who have a positive pregnancy test at the Screening visit or Day 1 or who intend to become pregnant or breastfeed during the study.
5. Individuals with a history of myocarditis, pericarditis, myopericarditis or cardiomyopathy.
6. Individuals with a history of Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis.
7. Individuals with a known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular (I.M.) injection.
8. Individuals with a history of congenital or acquired immunodeficiency.
9. Individuals who have received immunomodulatory, immunostimulatory, or immunosuppressant drugs including interferon and cytotoxic drugs within 3 months of Screening/Day 1 or who plan to receive them during the study.
10. Individuals requiring systemic corticosteroids exceeding 10 mg/day of prednisone equivalent for ≥10 days within 30 days of Screening. The use of topical, ophthalmic, inhaled, and intranasal steroid preparations will be permitted.
11. 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.
12. Individuals with an immunosuppressive or immunodeficient state, asplenia, or recurrent severe infections.
13. Individuals with a documented history of chronic infection including HIV, HBV, HCV, or who are currently known to have active tuberculosis.
14. Individuals with chronic illness that, in the opinion of the Investigator, are at a stage where it might interfere with trial participation or interpretation of study results.
15. Individuals receiving treatment with another investigational drug, biological agent, or device within 28 days of screening, or 5 half-lives of the investigational drug, whichever is longer; or are currently enrolled in or plan to participate in another clinical trial with an investigational agent during the study period.
16. Individuals who received any influenza vaccine within 6 months prior to enrollment. Individuals who plan to receive an influenza vaccine during the study period*.
17. 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.

18. 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.

    • Participants in the older adult group (Part 3) are allowed, following their Day 29 visit, to receive the authorized influenza vaccine as per country-specific recommendations.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 of ARCT-2138, younger adults; Dose Level 1 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: Cohort 2 of ARCT-2138, younger adults; Dose Level 2 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: Cohort 3 of ARCT-2138, younger adults; Dose Level 3 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: Cohort 4 of ARCT-2138, younger adults; Dose Level 4 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: Low Dose, younger and older adults; Low dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: Medium Dose, younger and older adults; Medium dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Experimental: High Dose, younger and older adults; High dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138	Biological: ARCT-2138; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Self-Amplifying RNA seasonal Influenza vaccine
Active Comparator: Control Dose, younger adults; Licensed Quadrivalent Vaccine administered through intramuscular injection in the deltoid muscle. Interventions: Control Vaccine: Licensed Quadrivalent Vaccine for younger adults	Biological: Licensed Quadrivalent Vaccine for younger adults; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Influenza vaccine, surface antigen, inactivated, prepared in cell cultures
Active Comparator: Control Dose, older adults; Licensed Quadrivalent Vaccine administered through intramuscular injection in the deltoid muscle. Interventions: Control Vaccine: Licensed Quadrivalent Vaccine for older adults	Biological: Licensed Quadrivalent Vaccine for older adults; Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.; Other Names: Influenza vaccine, surface antigen, inactivated, adjuvanted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants reporting local Adverse Events	Solicited local AEs include injection-site pain, erythema and swelling	14 Days following study vaccination
Percentage of participants reporting systemic Adverse Events	Solicited systemic AEs include fatigue, headache, myalgia, arthralgia, nausea, chills, and fever.	14 Days following study vaccination
Percentage of participants reporting unsolicited Adverse Events	Spontaneously reported adverse events and as elicited by investigational site staff	29 Days following study vaccination
Percentage of participants reporting laboratory or vital signs abnormalities	Abnormal clinically significant values	29 Days following study vaccination
Percentage of participants reporting serious adverse events, medically attended adverse events adverse events of special interest and adverse events leading early termination	Spontaneously reported adverse events and as elicited by investigational site staff	29 Days following study vaccination
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein.	HAI antibody levels expressed as GMT, GMFI, SCRs and HAI titers.	29 days following study vaccination
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins.	ELLA antibody levels expressed as GMT, GMFI, SCRs and HAI titers.	29 days following study 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 early termination	Spontaneously reported adverse events and as elicited by investigational site staff	181 days following study vaccination
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein.	HAI antibody levels expressed as GMT, GMFI, SCRs and HAI titers.	181 days following study vaccination
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins.	ELLA antibody levels expressed as GMT, GMFI, SCRs and HAI titers.	181 days following study vaccination

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 (Actual): January 22, 2024
• Primary Completion (Actual): August 10, 2024
• Study Completion (Actual): January 7, 2025

Study Registration Dates

• First Submitted: November 5, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Biological Factors; Physiological Phenomena; Biological Products; Complex Mixtures; Vaccines; Growth and Development; Viral Vaccines; Antigens; In Vitro Techniques; Culture Techniques; Influenza Vaccines; Aging; Antigens, Surface; Cell Culture Techniques
• Other Study ID Numbers: ARCT-2138-01

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