A Study to Investigate the Safety and Immunogenicity of the Quadrivalent Influenza mRNA Vaccines in Adults Aged 18 Years and Above

NCT06361875 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: VAV00045U1111-1295-2852
• Study Type: interventional
• Target: 908
• Locations: 3 countries
• Sites: 13

Brief Summary

The purpose of this study was to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of different formulations of Quadrivalent Influenza Vaccine (QIV) messenger ribonucleic acid (mRNA) (MRT5421, MRT5424, and MRT5429) compared to an active control (QIV- standard dose (SD), QIV- high dose (HD) \[adults ≥ 65 years of age only\], or quadrivalent recombinant influenza vaccine (RIV4)) in adults 18 years of age and older.

Conditions

Healthy Volunteers; Influenza Immunization

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) After Vaccine Administration

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination. Systemic AEs are all AEs that were not injection or administration site reactions. Immediate events are recorded to capture medically relevant unsolicited systemic AEs which occur within the first 30 minutes after vaccination.

  Within 30 minutes after vaccine administration on Day 1

• Number of Participants With Solicited Injection Site Reactions After Vaccine Administration

  An adverse reaction (AR) is any noxious and unintended response to a study vaccine related to any dose. Solicited injection site reactions are reactions at and around the injection site of the vaccine observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.

  Within 7 days after vaccine administration on Day 1

• Number of Participants With Solicited Systemic Reactions After Vaccine Administration

  An AR is any noxious and unintended response to a study vaccine related to any dose. Solicited systemic reactions are systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.

  Within 7 days after vaccine administration on Day 1

• Number of Participants With Unsolicited Adverse Events After Vaccine Administration

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination.

  Within 28 days after vaccine administration on Day 1

• Number of Participants With Medically Attended Adverse Events (MAAEs)

  An MAAE is a new onset or a worsening of a condition that prompts the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department.

  Within 180 days after vaccine administration on Day 1

• Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs)

  An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. An AESI (serious or non-serious) is 1 of scientific and medical concern specific to the Sponsor's study vaccine or program, for which ongoing monitoring and rapid communication by the investigator to the Sponsor can be appropriate. The AESIs was defined as anaphylactic reactions (including bronchospasms, and laryngeal spasms), Guillain-Barré syndrome, neuritis (including Bell's palsy), myocarditis, pericarditis, myopericarditis and vasculitis.

  From the vaccine administration (Day 1) until 12 months after vaccine administration, approximately 366 days

• Number of Participants With Abnormal Biological Test Results

  Blood samples were collected for the assessment of abnormal hematology and clinical chemistry parameters. Only participants with outside the normal range hematology and clinical chemistry parameters are reported.

  Within 8 days after vaccine administration on Day 1

• Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 1

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% confidence interval (CI) was based on the Clopper-Pearson method.

  Day 1

• Geometric Mean of Hemagglutination Inhibition Antibody Titer at Day 29

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI was based on the Clopper-Pearson method.

  Day 29

• Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 1

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.

  Day 1

• Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 29

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.

  Day 29

• Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 29

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Clopper-Pearson method.

  Days 1 and 29

• Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 29

  The seroconversion was defined as titer \<10 on Day 1 and post-injection titer \>=40 on Day 29; or defined as titer \>=10 on Day 1 and a \>=4-fold increase in titer on Day 29. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.

  Day 29

• Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 29

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.

  Day 29

• Percentage of Participants With >=2 and >=4 Fold Increase in Hemagglutination Inhibition Antibody Titer at Day 29

  The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.

  Days 1 and 29

Secondary Outcomes (3)

• Geometric Mean of Neutralization Test (NT) Antibody Titer at Days 1 and 29

  Days 1 and 29

• Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 29

  Days 1 and 29

• Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 29

  Days 1 and 29

Study Arms (10)

Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5421

Biological: Quadrivalent Influenza mRNA Vaccine MRT5421

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5424

Biological: Quadrivalent Influenza mRNA Vaccine MRT5424

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2

EXPERIMENTAL

participants received a single dose of QIV mRNA vaccine MRT5424

Biological: Quadrivalent Influenza mRNA Vaccine MRT5424

Quadrivalent Influenza SD Vaccine

ACTIVE COMPARATOR

participants received a single dose of QIV-SD vaccine

Biological: Quadrivalent Influenza Standard Dose Vaccine

Quadrivalent Influenza HD Vaccine

ACTIVE COMPARATOR

participants received a single dose of QIV -HD vaccine (for adults ≥ 65 years of age only)

Biological: Quadrivalent Influenza High-Dose Vaccine

Quadrivalent Influenza RIV4 Vaccine

ACTIVE COMPARATOR

participants received a single dose of RIV4 vaccine

Biological: Quadrivalent Recombinant Influenza Vaccine

Interventions

Quadrivalent Influenza mRNA Vaccine MRT5421 BIOLOGICAL

Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection

Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1

Quadrivalent Influenza mRNA Vaccine MRT5429 BIOLOGICAL

Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4

Quadrivalent Influenza High-Dose Vaccine BIOLOGICAL

Pharmaceutical form:suspension for injection in pre filled syringe -Route of administration:Intramuscular injection

Also known as: Fluzone High-Dose Quadrivalent®

Quadrivalent Influenza HD Vaccine

Quadrivalent Recombinant Influenza Vaccine BIOLOGICAL

Pharmaceutical form:suspension for injection in pre filled syringe-Route of administration:Intramuscular injection

Also known as: Flublok Quadrivalent®

Quadrivalent Influenza RIV4 Vaccine

Quadrivalent Influenza mRNA Vaccine MRT5424 BIOLOGICAL

Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1; Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2

Quadrivalent Influenza Standard Dose Vaccine BIOLOGICAL

Pharmaceutical form: suspension for injection in prefilled syringe -Route of administration:Intramuscular injection

Also known as: Fluzone Qudrivalent®

Quadrivalent Influenza SD Vaccine

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 was eligible to participate if she was not pregnant or breastfeeding and one of the following conditions applied:
• Was of non-childbearing potential. To be considered of non-childbearing potential, a female must of been postmenopausal for at least 1 year, or surgically sterile OR
• Was of childbearing potential and agreed 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 of had a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before the 1st dose of study intervention

You may not qualify if:

• 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, 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 vaccine
• Previous history of myocarditis, pericarditis, and / or myopericarditis
• Known history of previous episodes of Gillian-Barre Syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
• Participants with an ECG that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, 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, was at a stage where it might have interfered with study conduct or completion
• 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 was not included in the study until the condition was resolved or the febrile event subsided
• Participant who had acute infection symptoms or a positive SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the 1st visit (V01)
• Receipt of any vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine in the 4 weeks following study intervention administration
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
• Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration
• NOTE: The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (13)

California Research Foundation Site Number : 8400038

San Diego, California, 92123-1881, United States

Location

Indago Research and Health Center- Site Number : 8400032

Hialeah, Florida, 33012, United States

Location

Cenexel Research Centers of America- Site Number : 8400037

Hollywood, Florida, 33024, United States

Location

Brengle Family Medicine Site Number : 8400045

Indianapolis, Indiana, 46260, United States

Location

AMR Lexington- Site Number : 8400042

Lexington, Kentucky, 40509, United States

Location

Velocity Clinical Research- New Orleans Site Number : 8400053

New Orleans, Louisiana, 70119, United States

Location

The Alliance for Multispecialty Research - KCM, LLC- Site Number : 8400034

Kansas City, Missouri, 64114, United States

Location

Velocity Clinical Research Norfolk- Site Number : 8400046

Norfolk, Nebraska, 68701, United States

Location

AMR Knoxville- Site Number : 8400043

Knoxville, Tennessee, 37909, United States

Location

Clinical Trials of Texas, Inc. - PPDS- Site Number : 8400029

San Antonio, Texas, 78229, United States

Location

Cenexel JBR- Site Number : 8400051

Salt Lake City, Utah, 84107, United States

Location

Investigational Site Number : 3400001

San Pedro Sula, 21104, Honduras

Location

Investigational Site Number : 6300002

Barrio Sabana, 00694, Puerto Rico

Location

Related Links

• VAV00045 Plain Language Results Summary

MeSH Terms

Conditions

Influenza, Human

Interventions

Vaccines; Influenza Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Viral Vaccines

Limitations and Caveats

Due to internal project decisions made during the study, neutralizing antibody data was not collected. Therefore, no analysis was conducted for secondary outcome measures.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double-blind (Participants; Sites except for those preparing/administering study intervention; Sponsor's except Sponsor unblinded internal safety review committee)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel with dose escalation for sentinel cohort

Study Record Dates

• First Submitted: April 4, 2024
• First Posted: April 12, 2024
• Study Start: April 1, 2024
• Primary Completion: June 9, 2025
• Study Completion: June 9, 2025
• Last Updated: August 4, 2026
• Results First Posted: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

HO (1); PR (1); US (11)