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

NCT05829356 | Completed Phase 1

• 2 other identifiers: VAV00019U1111-1278-3835
• Study Type: interventional
• Target: 159
• Locations: 2 countries
• Sites: 8

Brief Summary

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).

Conditions

Influenza Immunization

Outcome Measures

Primary Outcomes (17)

• Number of participants with immediate adverse events (AEs)

  Unsolicited systemic AEs that occur within 30 minutes after vaccination

  Within 30 minutes after vaccination

• Number of participants with solicited injection site or systemic reaction

  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

  Within 7 days from vaccination

• Number of participants with unsolicited adverse events

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

  Up to 28 days after injection

• Presence of out-of-range biological test results

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

  At Day 3, Day 9 or Day 29

• Presence of serious adverse events (SAEs)

  Number of participants experiencing SAEs

  Throughout Study (up to approximately Month 6)

• Presence of adverse events of special interest (AESIs)

  Number of participants experiencing AESIs

  Throughout Study (up to approximately Month 6)

• Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain

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

  Day 29

• HAI titers at D01

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

  Day 1

• HAI titers at D29

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

  Day 29

• Individual HAI Ab titer ratio

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

  Day 1 through Day 29

• Number of Participants with Vaccine Response or Seroconversion

  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)

  Day 1 through Day 29

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

  Expressed as percentage post-baseline

  Day 1 to Day 29

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

  Day 29

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

  Nab titers at Day 1

  Day 1

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

  Nab titers at Day 29

  Day 29

• Individual nab titer ratio

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

  Day 1 through Day 29

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

  Expressed as percentage post-baseline

  Day 1 to Day 29

Study Arms (6)

Group 1: H3 mRNA /LNP dose 1

EXPERIMENTAL

Participants will receive one intramuscular (IM) dose of H3 mRNA/LNP at Day 01

Biological: H3 mRNA / LNP Vaccine

Group 2: H3 mRNA /LNP dose 2

EXPERIMENTAL

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Biological: H3 mRNA / LNP Vaccine

Group 3: H3 mRNA /LNP dose 3

EXPERIMENTAL

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Biological: H3 mRNA / LNP Vaccine

Group 4: H3 mRNA /LNP dose 4

EXPERIMENTAL

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Biological: H3 mRNA / LNP Vaccine

Group 5: H3 mRNA /LNP dose 5

EXPERIMENTAL

Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Biological: H3 mRNA / LNP Vaccine

Group 6 (Control Group): RIV4 dose

ACTIVE COMPARATOR

Participants will receive one IM dose of RIV4 at Day 01

Biological: Quadrivalent recombinant influenza Vaccine (RIV4)

Interventions

H3 mRNA / LNP Vaccine BIOLOGICAL

Pharmaceutical Form: Suspension for injection Route of Administration: Intra-Muscular

Group 1: H3 mRNA /LNP dose 1; Group 2: H3 mRNA /LNP dose 2; Group 3: H3 mRNA /LNP dose 3; Group 4: H3 mRNA /LNP dose 4; Group 5: H3 mRNA /LNP dose 5

Quadrivalent recombinant influenza Vaccine (RIV4) BIOLOGICAL

Pharmaceutical Form: Solution for injection in a pre-filled syringe Route of Administration: Intra-Muscular

Also known as: Flublok Quadravalent®

Group 6 (Control Group): RIV4 dose

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (8)

Investigational Site Number : 0360004

Herston, Queensland, 4006, Australia

Location

Investigational Site Number : 0360001

Morayfield, Queensland, 4506, Australia

Location

Investigational Site Number : 0360002

Camberwell, Victoria, 3124, Australia

Location

Investigational Site Number : 0360003

Adelaide, 5000, Australia

Location

Investigational Site Number : 8260002

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Investigational Site Number : 8260001

London, London, City of, SW10 9NH, United Kingdom

Location

Investigational Site Number : 8260004

London, London, City of, W12 0HS, United Kingdom

Location

Investigational Site Number : 8260003

Sheffield, Sheffield, S10 2JF, United Kingdom

Location

Related Links

• VAV00019 Plain Language Results Summary

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study will be blinded to participants and sites (except for those preparing/administering study interventions. The sponsor will be unblinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: April 25, 2023
• Study Start: April 12, 2023
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (4); AU (4)