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NCT Number: NCT06602531

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

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Key information

Conditions

Influenza, Human Infections Orthomyxoviridae Infections RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Velocity Clinical Research, La Mesa, California, United States

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ARCT-2304

Biological

Each participant will receive 2-dose regimen intramuscular (IM) dose into the deltoid muscle.

Other names: Self-Amplifying mRNA pandemic Influenza vaccine

Control vaccine younger adults

Biological

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

Other names: Influenza vaccine

Control vaccine older adults

Biological

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

Other names: Influenza vaccine

Placebo Vaccine

Other

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

Other names: saline

Primary outcomes

  1. Number of Participants With Solicited Adverse Events (AEs) Within 7 Days After Each Vaccination

    Time frame: 7 days post each dose

    The following solicited local and systemic AEs were recorded from Day 1 to 7 days after each vaccination (dose): Injection site pain, Erythema, Swelling, Fatigue, Headache, Myalgia, Arthralgia, Dizziness, Nausea, Chills, Fever (≥100.4 °Fahrenheit [F] /≥38.0 °Celsius [C]). A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section.

  2. Number of Participants With Unsolicited AEs Within 28 Days After Each Vaccination

    Time frame: D1,29 Cohorts: up to Day 29 and up to Day 57 (28 days post each dose), D1,57 Cohorts: up to Day 29 and up to Day 85 (28 days post each dose)

    An AE was any untoward medical occurrence in a participant or participant administered a medicinal product, whether or not considered related to the trial vaccine. An unsolicited AE was defined as any AE not included in the list of solicited AEs (i.e., any event other than injection site pain, erythema, swelling, fatigue, headache, myalgia, arthralgia, dizziness, nausea, chills, or fever (≥100.4 °F / ≥38.0 °C). Solicited AEs that lasted for more than 7 days were considered as unsolicited AEs. Unsolicited AEs were recorded from Day 1 up to 28 days after each vaccination (dose). A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section'.

  3. Number of Participants With Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), AEs of Special Interest (AESIs), and AEs Leading To Early Termination From Day 1 to 28 Days After Second Vaccination

    Time frame: D1,29 Cohorts: up to Day 57, D1,57 Cohorts: up to Day 85

    An SAE was defined as any AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity, or required inpatient hospitalization or prolongation of existing hospitalization. AEs potentially associated with messenger ribonucleic acid (mRNA) vaccines and influenza vaccines were reported as AESIs. MAAEs were defined as AEs with medically attended visits including hospital, emergency room, urgent care clinic, or other visits (including phone/telehealth visits) to or from medical personnel for any reason but did not fulfil seriousness criteria. A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section'.

  4. Geometric Mean Titer of Antibody Response to Hemagglutinin (HA) Glycoprotein Measured By Hemagglutinin Inhibition (HAI) Assay

    Time frame: D1,29 Cohorts: Day 1, Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 1, Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Antibody titers were expressed as Geometric Mean Titers.

  5. Geometric Mean Titer of Antibody Response to Neuraminidase (NA) Glycoprotein Measured By Enzyme-linked Lectin Assay (ELLA)

    Time frame: D1,29 Cohorts: Day 1, Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 1, Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Antibody titers were expressed as Geometric Mean Titers.

  6. Geometric Mean Fold Rise of Antibody Response to HA Glycoprotein Measured By HAI Assay

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Geometric Mean Fold Rise was reported as a ratio to Day 1.

  7. Geometric Mean Fold Rise of Antibody Response to NA Glycoprotein Measured By ELLA

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Geometric Mean Fold Rise was reported as a ratio to Day 1.

  8. Percentage of Participants With Seroconversion of Antibody Response to HA Glycoprotein Measured By HAI Assay

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Seroconversion was recorded if participant had pre-vaccination antibody titer < Lower Limit Of Quantitation (LLOQ) and a post-vaccination antibody titer ≥ 4 x LLOQ, or a pre-vaccination antibody titer ≥LLOQ and a ≥4-fold increase in post-vaccination antibody titer.

  9. Percentage of Participants With Seroconversion of Antibody Response to NA Glycoprotein Measured By ELLA

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Seroconversion was recorded if participant had pre-vaccination antibody titer < LLOQ and a post-vaccination antibody titer ≥ 4 x LLOQ, or a pre-vaccination antibody titer ≥LLOQ and a ≥4-fold increase in post-vaccination antibody titer.

  10. Percentage of Participants With HAI Titers Above or Equal to Prespecified Thresholds

    Time frame: D1,29 Cohorts: Day 57 (28 days post dose 2), D1,57 Cohorts: Day 85 (28 days post dose 2)

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. The prespecified antibody threshold levels were as follows: ≥1:10, ≥1:20, ≥1:40, ≥1:80, ≥1:160, and ≥1:320.

  11. Percentage of Participants With ELLA Titers Above or Equal to Prespecified Thresholds

    Time frame: D1,29 Cohorts: Day 57 (28 days post dose 2), D1,57 Cohorts: Day 85 (28 days post dose 2)

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. The prespecified antibody threshold levels were as follows: ≥1:10, ≥1:20, ≥1:40, ≥1:80, ≥1:160, and ≥1:320.

Secondary outcomes

  1. Number of Participants With SAEs, MAAEs, AESIs, and AEs Leading To Early Termination From Day 1 to Day 240

    Time frame: Day 1 to Day 240

    A SAE was defined as any AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity, or required inpatient hospitalization or prolongation of existing hospitalization. AEs potentially associated with mRNA vaccines and influenza vaccines were reported as AESIs. MAAEs were defined as AEs with medically attended visits including hospital, emergency room, urgent care clinic, or other visits (including phone/telehealth visits) to or from medical personnel for any reason, but did not fulfil seriousness criteria. A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section.

  2. Geometric Mean Titer of Antibody Response To HA Glycoprotein Measured By HAI Assay at Day 240

    Time frame: Day 240

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Antibody titers were expressed as Geometric Mean Titers.

  3. Geometric Mean Titer of Antibody Response to NA Glycoprotein Measured By ELLA at Day 240

    Time frame: Day 240

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Antibody titers were expressed as Geometric Mean Titers.

  4. Geometric Mean Fold Rise of Antibody Response to HA Glycoprotein Measured By HAI Assay at Day 240

    Time frame: Day 240

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Geometric Mean Fold Rise was reported as a ratio to Day 1.

  5. Geometric Mean Fold Rise of Antibody Response to NA Glycoprotein Measured By ELLA at Day 240

    Time frame: Day 240

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Geometric Mean Fold Rise was reported as a ratio to Day 1.

  6. Percentage of Participants With Seroconversion of Antibody Response to HA Glycoprotein Measured By HAI Assay At Day 240

    Time frame: Day 240

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Seroconversion was recorded if participant had pre-vaccination antibody titer < LLOQ and a post-vaccination antibody titer ≥ 4 x LLOQ, or a pre-vaccination antibody titer ≥LLOQ and a ≥4-fold increase in post-vaccination antibody titer.

  7. Percentage of Participants With Seroconversion of Antibody Response to NA Glycoprotein Measured By ELLA At Day 240

    Time frame: Day 240

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. Seroconversion was recorded if participant had pre-vaccination antibody titer < LLOQ and a post-vaccination antibody titer ≥ 4 x LLOQ, or a pre-vaccination antibody titer ≥LLOQ and a ≥4-fold increase in post-vaccination antibody titer.

  8. Percentage of Participants With HAI Titers Above Or Equal To Prespecified Thresholds At Day 240

    Time frame: Day 240

    A serum HAI assay was used for measuring HA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. The prespecified antibody threshold levels were as follows: ≥1:10, ≥1:20, ≥1:40, ≥1:80, ≥1:160, and ≥1:320.

  9. Percentage of Participants With ELLA Titers Above Or Equal to Prespecified Thresholds At Day 240

    Time frame: Day 240

    A serum ELLA assay was used for measuring NA-specific antibodies against the A/H5N1/Indonesia/5/2005 influenza strain. The prespecified antibody threshold levels were as follows: ≥1:10, ≥1:20, ≥1:40, ≥1:80, ≥1:160, and ≥1:320.

  10. Geometric Mean Titer of Antibody Response Against HA Glycoprotein Measured By Microneutralization (MN) Assay

    Time frame: D1,29 Cohorts: Day 1, Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 1, Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    Neutralizing antibody response to H5 hemagglutinin was measured by MN assay. Antibody titers were expressed as Geometric Mean Titers.

  11. Geometric Mean Fold Rise of Antibody Response to HA Glycoprotein Measured By MN Assay

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    Neutralizing antibody response to H5 hemagglutinin was measured by MN assay. Geometric Mean Fold Rise was reported as a ratio to Day 1.

  12. Percentage of Participants With Seroconversion of Antibody Response to HA Glycoprotein Measured By MN Assay

    Time frame: D1,29 Cohorts: Day 29 (28 days post dose 1), Day 36 (7 days post dose 2), and Day 57 (28 days post dose 2), D1,57 Cohorts: Day 57 (56 days post dose 1), Day 64 (7 days post dose 2), and Day 85 (28 days post dose 2)

    Neutralizing antibody response to H5 hemagglutinin was measured by MN assay. Seroconversion was recorded if participant had pre-vaccination antibody titer < LLOQ and a post-vaccination antibody titer ≥ 4 x LLOQ, or a pre-vaccination antibody titer ≥LLOQ and a ≥4-fold increase in post-vaccination antibody titer.

  13. Percentage of Participants With MN Titers Above Or Equal To Prespecified Thresholds

    Time frame: D1,29 Cohorts: Day 57 (28 days post dose 2), D1,57 Cohorts: Day 85 (28 days post dose 2)

    Neutralizing antibody response to H5 hemagglutinin was measured by MN assay. The prespecified antibody threshold levels were as follows: ≥1:10, ≥1:20, ≥1:40, ≥1:80, ≥1:160, and ≥1:320.

Sponsors and collaborators

Lead sponsor

Arcturus Therapeutics, Inc.

Industry

Collaborators

  • Biomedical Advanced Research and Development Authority

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Sep 19, 2024
Registry last updated
Sep 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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