Influenza Immunization, Healthy Volunteers
Conditions
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.
Detailed description
Study duration per participant was approximately 12 months. * Treatment duration: 1 injection of one of the 7 QIV mRNA or one of the controls * Dose escalation with sequential enrollment
Interventions
BIOLOGICALQuadrivalent Influenza mRNA Vaccine MRT5421
Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection
BIOLOGICALQuadrivalent Influenza mRNA Vaccine MRT5424
Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection
BIOLOGICALQuadrivalent Influenza mRNA Vaccine MRT5429
Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection
Pharmaceutical form: suspension for injection in prefilled syringe -Route of administration:Intramuscular injection
BIOLOGICALQuadrivalent Influenza High-Dose Vaccine
Pharmaceutical form:suspension for injection in pre filled syringe -Route of administration:Intramuscular injection
Pharmaceutical form:suspension for injection in pre filled syringe-Route of administration:Intramuscular injection
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Modified double-blind (Participants; Sites except for those preparing/administering study intervention; Sponsor's except Sponsor unblinded internal safety review committee)
Intervention model description
Parallel with dose escalation for sentinel cohort
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Aged from 18 years on the day of inclusion or aged from 21 years on the days of inclusion, depending on the countries. * 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
Exclusion criteria
Participants were excluded from the study if any of the following criteria applied: * 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 * 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, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) After Vaccine Administration | Within 30 minutes after vaccine administration on Day 1 | 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. |
| Number of Participants With Solicited Injection Site Reactions After Vaccine Administration | Within 7 days after vaccine administration on Day 1 | 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. |
| Number of Participants With Solicited Systemic Reactions After Vaccine Administration | Within 7 days after vaccine administration on Day 1 | 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. |
| Number of Participants With Unsolicited Adverse Events After Vaccine Administration | Within 28 days after vaccine administration on Day 1 | 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. |
| Number of Participants With Medically Attended Adverse Events (MAAEs) | Within 180 days after vaccine administration on Day 1 | 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. |
| Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs) | From the vaccine administration (Day 1) until 12 months after vaccine administration, approximately 366 days | 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. |
| Number of Participants With Abnormal Biological Test Results | Within 8 days after vaccine administration on Day 1 | 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. |
| Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 1 | 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. |
| Geometric Mean of Hemagglutination Inhibition Antibody Titer at Day 29 | 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. |
| Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 1 | 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. |
| Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 29 | 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. |
| Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 29 | Days 1 and 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. |
| Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 29 | 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. |
| Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 29 | 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. |
| Percentage of Participants With >=2 and >=4 Fold Increase in Hemagglutination Inhibition Antibody Titer at Day 29 | Days 1 and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean of Neutralization Test (NT) Antibody Titer at Days 1 and 29 | Days 1 and 29 | The NT Ab was planned to be measured using seroneutralization (SN) measurement method. The 95% CI was planned to be calculated using the Clopper-Pearson method. |
| Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 29 | Days 1 and 29 | The NT Ab was planned to be measured using SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination was planned to be reported. The 95% CI was planned to be calculated using the Clopper-Pearson method. |
| Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 29 | Days 1 and 29 | The NT Ab was planned to be measured using SN measurement method. The 95% CI for the single percentage was planned to be calculated using the Clopper-Pearson method. |
Countries
Honduras, Puerto Rico, United States
Participant flow
Recruitment details
The study was conducted at 19 centers in 2 countries from 01 April 2024 to 09 June 2025. QIV mRNA= Quadrivalent influenza modified messenger ribonucleic acid vaccine; QIV-SD= Standard dose quadrivalent influenza vaccine; RIV4= Quadrivalent recombinant influenza vaccine; QIV-HD= High dose quadrivalent influenza vaccine.
Pre-assignment details
A total of 908 participants were enrolled and randomized in the study. Randomization was stratified by cohort and age group (18 to 64 years and \>= 65 years). Participants were assigned to either QIV mRNA groups, QIV-SD, RIV4 or QIV-HD (only for participants aged 65 years and above) in a ratio of allocation between 2 groups as 1:1 or 1:2.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 16.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants |
| Race/Ethnicity, Customized Mixed Origin | 2 Participants |
| Race/Ethnicity, Customized Not Reported | 4 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 28 Participants |
| Sex: Female, Male Female | 480 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 1 / 120 | 0 / 118 | 0 / 120 | 0 / 117 | 0 / 27 | 0 / 75 | 0 / 119 | 0 / 119 | 1 / 60 |
| other Total, other adverse events | 18 / 28 | 81 / 120 | 87 / 118 | 91 / 120 | 84 / 117 | 21 / 27 | 57 / 75 | 38 / 119 | 27 / 119 | 24 / 60 |
| serious Total, serious adverse events | 0 / 28 | 4 / 120 | 2 / 118 | 3 / 120 | 0 / 117 | 0 / 27 | 1 / 75 | 2 / 119 | 4 / 119 | 1 / 60 |
Outcome results
None listed