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Completed

NCT Number: NCT05829356

Substudy 01 - Safety and Immunogenicity of One Monovalent Modified mRNA Vaccine Encoding Influenza Hemagglutinin With LNP, in Adult Participants Aged 18 to 49 Years and 60 Years and Above

This is a Phase 1, parallel, randomized, active-controlled, multi-center, dose-esclation study with a Master Protocol design which will include several substudies that are developed to evaluate the safety and immunogenicity of different dose levels of modified messenger ribonucleic acid (mRNA) vaccines encoding full length hemagglutinin (HA) sequence of influenza virus encapsulated in lipid nanoparticles (LNPs) (hereafter referred to as HA mRNA vaccines) compared to control(s). The HA mRNA vaccine candidates and control(s) are presented in the substudy protocols.

The aim is to generate clinical data across different substudies to provide learnings regarding the mRNA technology to support optimization of the mRNA platform including mRNA and LNP design and to support the decision of LNP and dose selection for future projects using mRNA technology.

The purpose of this Substudy 01 is to evaluate the safety and immunogenicity of a single IM injection of up to 5 dose levels of a monovalent modified mRNA encoding the full-length HA sequence of A/Tasmania/503/2020 (H3N2) influenza virus encapsulated in LNP (hereafter referred to as H3 mRNA /LNP) administered as a single intramuscular (IM) injection in adults 18 to 49 years of age and 60 years of age and above, compared to the following active control: a quadrivalent recombinant influenza vaccine (RIV4).

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigational Site Number : 0360004, Herston, Queensland, Australia

Loading trial locations.

About this study

The study duration per participant will be approximately 6 months with 1 injection of one of the different HA mRNA vaccines or control for each substudy and a dose-escalation with sequential enrollment (sentinel cohort followed by main cohort).

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Aged 18 years and above on the day of inclusion

*Aged 18 years to 49 years or 60 years and above on the day of inclusion (substudy 01)

  • A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
  • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile.

OR

  • Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.
  • A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) at the screening visit.
  • Inclusion Criteria to be Checked at Visit 1 (Day 1)

Participants are eligible for the study only if all of the following criteria are met:

A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

  • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile.

OR

  • Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.

A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before the first dose of study intervention.

Exclusion criteria

  • Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
  • Any screening laboratory parameter with laboratory abnormalities that are greater than Grade 1 or deemed clinically significant in the opinion of the Investigator
  • OR, any screening Liver Function Test (ALT, AST, Bilirubin) > 1.2x Upper Limit of Normal or any other screening laboratory parameter outside of the range of normal limits for age and gender
  • Positive test for human immunodeficiency virus (HIV) antigen and/or antibodies (Abs), hepatitis B (HB) virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs)
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
  • Known systemic hypersensitivity to any of the study intervention components (eg, polyethylene glycol [PEG], polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA COVID-19 vaccine
  • Previous history of myocarditis, pericarditis, and/or myopericarditis
  • Screening electrocardiogram (ECG) or troponin value that is consistent with probable or possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that demonstrates clinically relevant abnormalities that may affect participant safety or study results
  • Self-reported thrombocytopenia, contraindicating intramuscular vaccination based on Investigator's judgment
  • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination based on Investigator's judgment
  • Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
  • Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
  • Receipt of any vaccine in the 4 weeks preceding study enrollment or planned receipt of any vaccine in the 4 weeks following study intervention administration
  • Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or planned receipt of any mRNA vaccine/product within the 2 months following study intervention administration
  • Receipt of immune globulins, blood or blood-derived products in the past 3 months -Participation at the time of study enrollment (or in the 4 weeks preceding study enrollment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
  • Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
  • Exclusion criteria to be checked at Visit 1 Day 1:
  • Moderate or severe acute illness/infection (according to Investigator's judgment) or febrile illness (temperature ≥ 38.0°C [100.4°F]) on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Treatment and study plan

H3 mRNA / LNP Vaccine

Biological

Pharmaceutical Form: Suspension for injection

Route of Administration: Intra-Muscular

Quadrivalent Recombinant Influenza Vaccine (RIV4)

Biological

Pharmaceutical Form: Solution for injection in a pre-filled syringe

Route of Administration: Intra-Muscular

Other names: Flublok Quadravalent®

Primary outcomes

  1. Number of participants with immediate adverse events (AEs)

    Time frame: Within 30 minutes after vaccination

    Unsolicited systemic AEs that occur within 30 minutes after vaccination

  2. Number of participants with solicited injection site or systemic reaction

    Time frame: Within 7 days from vaccination

    Number of participants reporting Adverse reactions pre-listed in the protocol and case report form (CRF)

    • Injection site reactions: pain, redness, swelling
    • Systemic reactions: fever, headache, malaise, myalgia, arthralgia, chills

  3. Number of participants with unsolicited adverse events

    Time frame: Up to 28 days after injection

    Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions

  4. Presence of out-of-range biological test results

    Time frame: At Day 3, Day 9 or Day 29

    Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)

  5. Presence of serious adverse events (SAEs)

    Time frame: Throughout Study (up to approximately Month 6)

    Number of participants experiencing SAEs

  6. Presence of adverse events of special interest (AESIs)

    Time frame: Throughout Study (up to approximately Month 6)

    Number of participants experiencing AESIs

  7. Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain

    Time frame: Day 29

    Antibody are expressed as geometric mean titers (GMTs) at baseline and post-baseline

  8. HAI titers at D01

    Time frame: Day 1

    Antibody titers are expressed as GMTs at baseline and post-baseline

  9. HAI titers at D29

    Time frame: Day 29

    Antibody titers are expressed as GMTs at baseline and post-baseline

  10. Individual HAI Ab titer ratio

    Time frame: Day 1 through Day 29

    Individual HAI Ab titer ratio will be calculated as: D29/D01

  11. Number of Participants with Vaccine Response or Seroconversion

    Time frame: Day 1 through Day 29

    Seroconversion (HAI Ab titer < 10 [1/dil] at D01 and post-injection titer ≥ 40 [1/dil] at D29, or titer ≥ 10 [1/dil] at D01 and a ≥ 4-fold increase in titer [1/dil] at D29)

  12. 2-fold and 4-fold rise in HAI titers from D01 to D29

    Time frame: Day 1 to Day 29

    Expressed as percentage post-baseline

  13. Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 40 [1/dil]

    Time frame: Day 29

  14. Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 1

    Time frame: Day 1

    Nab titers at Day 1

  15. Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 29

    Time frame: Day 29

    Nab titers at Day 29

  16. Individual nab titer ratio

    Time frame: Day 1 through Day 29

    Individual nab titer ratio will be calculated as: D29/D01

  17. 2-fold and 4-fold increase in neutralizing Ab titers from D01 to D29

    Time frame: Day 1 to Day 29

    Expressed as percentage post-baseline

Sponsors and collaborators

Lead sponsor

Sanofi Pasteur, a Sanofi Company

Industry

Registry information

Official study title

A Phase I, Parallel, Randomized, Active-controlled, Multi-center, Dose-escalation Study With Early Safety Data Reviews to Assess Safety and Immunogenicity of One Monovalent Modified Influenza mRNA Vaccine Encapsulated in LNP, in Adults Aged 18 to 49 Years and 60 Years and Above.

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Apr 25, 2023
Registry last updated
Sep 12, 2025

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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