Influenza Immunization
Conditions
Brief summary
The purpose of this study is 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 is 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 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 1st dose of study intervention
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * 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, is at a stage where it might interfere 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 should not be included in the study until the condition has resolved or the febrile event has 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HAI Ab titer ≥ 40 (1/dil) | Day 29 | HAI Ab titer ≥ 40 (1/dil) at D29 |
| Number of participants with adverse events of special interests (AESIs) | Throughout the study (approximately 12 months) | AESIs reported throughout the study |
| Seroconversion | At Day 1 and Day 29 | Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-vaccination titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold-rise in titer \[1/dil\] at Day 29 |
| Geometric Mean of individual Titer Ratio (GMTR) | At Day 1 and Day 29 | Individual HAI Ab titer ratio D29/D01 |
| Number of participants with out-of-range biological test results | Up to 8 days after injection | Out-of-range biological test results (including shift from baseline values) |
| Geometric Mean Titer (GMT) | At Day 1 and Day 29 | Hemagglutinin inhibition (HAI) antibody (Ab) titers at D01 and D29 |
| Number of participants with immediate unsolicited systemic adverse events (AEs) | Within 30 minutes after injection | Unsolicited systemic AEs that occur within 30 minutes after vaccination |
| Number of participants with solicited injection site reactions | Up to 7 days after injection | Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: Injection site pain, Injection site erythema, and Injection site swelling |
| Number of participants with solicited systemic reactions | Up to 7 days after injection | Adverse reactions pre-listed in the protocol and case report form (CRF) Systemic reactions: fever, headache, fatigue, myalgia, arthralgia, chills |
| Number of participants with unsolicited AEs | Up to 28 days after injection | AEs that do not fulfill the conditions of solicited reactions |
| Number of participants with medically attended adverse events (MAAEs) | Up to 180 days after injection | MAAEs reported up to 180 days after injection |
| Number of participants with serious adverse events (SAEs) | Throughout the study (approximately 12 months) | SAEs reported throughout the study |
| AESIs reported throughout the study | AESIs reported throughout the study (approximatley 12 months) | AESIs reported throughout the study (approximately 12 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing Ab titers at D01 and D29 | At Day 1 and Day 29 | Neutralizing Ab titers at D01 and D29 |
| Individual neutralizing antibodies titer ratio | At Day 1 and Day 29 | Individual neutralizing antibodies titer ratio D29/D01 |
| 2-fold and 4-fold increase in neutralizing titers | Day 1 through Day 29 | 2-fold and 4-fold increase in neutralizing titers |
Countries
Honduras, Puerto Rico, United States
Outcome results
None listed