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

NCT06125691 | Completed Phase 1 DMC

• 1 other identifier: ARCT-2138-01
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Influenza, Human

Keywords

Influenza; Vaccine

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (3)

• Percentage of participants reporting serious adverse events, medically attended adverse events adverse events of special interest and adverse events leading early termination

  181 days following study vaccination

• Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein.

  181 days following study vaccination

• Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins.

  181 days following study vaccination

Study Arms (9)

Cohort 1 of ARCT-2138, younger adults

EXPERIMENTAL

Dose Level 1 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Cohort 2 of ARCT-2138, younger adults

EXPERIMENTAL

Dose Level 2 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Cohort 3 of ARCT-2138, younger adults

EXPERIMENTAL

Dose Level 3 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Cohort 4 of ARCT-2138, younger adults

EXPERIMENTAL

Dose Level 4 of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Low Dose, younger and older adults

EXPERIMENTAL

Low dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Medium Dose, younger and older adults

EXPERIMENTAL

Medium dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

High Dose, younger and older adults

EXPERIMENTAL

High dose level of ARCT-2138 administered through intramuscular injection in the deltoid muscle. Interventions: Investigational Vaccine: ARCT-2138

Biological: ARCT-2138

Control Dose, younger adults

ACTIVE COMPARATOR

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

Control Dose, older adults

ACTIVE COMPARATOR

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

Interventions

ARCT-2138 BIOLOGICAL

Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.

Also known as: Self-Amplifying RNA seasonal Influenza vaccine

Cohort 1 of ARCT-2138, younger adults; Cohort 2 of ARCT-2138, younger adults; Cohort 3 of ARCT-2138, younger adults; Cohort 4 of ARCT-2138, younger adults; High Dose, younger and older adults; Low Dose, younger and older adults; Medium Dose, younger and older adults

Licensed Quadrivalent Vaccine for younger adults BIOLOGICAL

Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.

Also known as: Influenza vaccine, surface antigen, inactivated, prepared in cell cultures

Control Dose, younger adults

Licensed Quadrivalent Vaccine for older adults BIOLOGICAL

Each participant will receive one 0.5 mL intramuscular (IM) dose into the deltoid muscle.

Also known as: Influenza vaccine, surface antigen, inactivated, adjuvanted

Control Dose, older adults

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals are male, female, or transgender adults 18 to 49 years of age or 65 to 85 years of age.
• 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.
• Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
• Individuals who have not received influenza vaccine within 6 months prior to enrollment.
• 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).
• Individuals of childbearing potential must be willing to adhere to contraceptive requirements.

You may not qualify if:

• 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.
• 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.
• 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 who have a positive pregnancy test at the Screening visit or Day 1 or who intend to become pregnant or breastfeed during the study.
• Individuals with a history of myocarditis, pericarditis, myopericarditis or cardiomyopathy.
• Individuals with a history of Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis.
• Individuals with a known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular (I.M.) injection.
• Individuals with a history of congenital or acquired immunodeficiency.
• 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.
• 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.
• 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.
• Individuals with an immunosuppressive or immunodeficient state, asplenia, or recurrent severe infections.
• Individuals with a documented history of chronic infection including HIV, HBV, HCV, or who are currently known to have active tuberculosis.
• 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.
• 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.

Sponsors & Collaborators

• Arcturus Therapeutics, Inc.: lead
• Seqirus: collaborator
• Novotech (Australia) Pty Limited: collaborator

Study Sites (2)

Nucleus Network Brisbane Clinic

Brisbane, Queensland, Australia

Location

Emeritus Research Camberwell

Melbourne, Victoria, 3124, Australia

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; Antigens, Surface; Cell Culture Techniques; Aging

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Culture Techniques; In Vitro Techniques; Growth and Development; Physiological Phenomena

Study Officials

• Clinical Program Director

  Arcturus Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Open Label (Part 4 only)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2023
• First Posted: November 9, 2023
• Study Start: January 22, 2024
• Primary Completion: August 10, 2024
• Study Completion: January 7, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)