Influenza, Healthy Volunteers
Conditions
Keywords
influenza, flu, vaccine, hexavalent
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular injection of different formulations of a hexavalent influenza messenger ribonucleic acid (mRNA) vaccine composed of differing dose levels of trivalent (TIV) mRNA hemagglutinin (HA) in combination with TIV mRNA-neuraminidase (NA) compared to an active control ((Fluzone standard-dose quadrivalent influenza vaccine (QIV-SD) or Fluzone high-dose quadrivalent influenza vaccine (QIV-HD) in adults 50 years of age and older.
Detailed description
Study details include the following: * Study Duration: approximately 12 months for each participant * Treatment: 1 injection of hexavalent vaccine, trivalent vaccine, or active control * Visit frequency: Day (D) 01, D03, D09, D29, and D181; D366 (telephone call) * Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort
Interventions
BIOLOGICALTrivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1
* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection
BIOLOGICALTIV mRNA-neuraminidase (NA)
* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection
BIOLOGICALTIV mRNA-HA Vaccine 2
* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection
* Pharmaceutical form: Liquid suspension for injection in pre-filled syringe * Route of administration: Intramuscular injection
BIOLOGICALQuadrivalent Influenza Vaccine High Dose
* Pharmaceutical form: Liquid 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
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Modified double-blind (participants; sites, except for those preparing/administering study intervention; and Sponsor will be blinded. Sponsor's internal safety monitoring team could be unblinded if necessary)
Intervention model description
Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participant aged 50 years on the day of inclusion * 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 prior to administration of study intervention.
Exclusion criteria
Participants are not eligible for the study if any of the following criteria are met: * 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 Guillain-Barré syndrome, neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis * Participants with an electrocardiogram 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 (IM) vaccination based on Investigator's judgment * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM 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 judgement) 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. * Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion * Participant who had acute infectious symptoms or a positive SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the first 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 or planned receipt of any mRNA vaccine in the 2 months after study vaccination * Participation at the time of study enrollment (or in the 4 weeks preceding study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure * Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-fold and 4-fold rise in NAI titers | Day 1 to Day 29 | 2-fold and 4-fold rise in NAI titers from D01 to D29 |
| Individual NAI Ab titer ratio D29/D01 | At Day 1 and Day 29 | Individual NAI Ab titer ratio D29/D01 |
| Seroconversion (NAI Ab titer) | At Day 1 and Day 29 | Number of participants with NAI 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) |
| NAI Ab titer ≥ 40 (1/dil) | At Day 29 | NAI Ab titer ≥ 40 (1/dil) at D29 |
| Number of participants with adverse events of special interest (AESIs) | AESIs throughout the study (Up to approximately 12 months) | Throughout the study |
| Number of participants with solicited injection site reactions | Up to 7 days after injection | Solicited injection site reactions pre-listed in the participant diary and in the case report form CRF |
| Number of participants with solicited systemic reactions | Up to 7 days after injection | Solicited systemic reactions pre-listed in the participant diary and in the CRF |
| 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) | SAEs throughout the study (Up to approximately 12 months) | Throughout the study |
| 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 out-of-range biological test results | Up to 8 days after injection | Out-of-range biological test results (including shift from baseline values) |
| Hemagglutinin inhibition (HAI) titers | At Day 1 and Day 29 | HAI titers at D01 and D29 |
| Individual HAI antibody (Ab) titer ratio D29/D01 | At Day 1 and Day 29 | Individual HAI Ab titer ratio D29/D01 |
| Seroconversion (HAI Ab titer) | At Day 1 and Day 29 | Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-injection titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold increase in titer \[1/dil\] at Day 29 |
| HAI Ab titer ≥ 40 (1/dil) | At Day 29 | HAI Ab titer ≥ 40 (1/dil) at D29 |
| Neuraminidase inhibition (NAI) titers | At Day 1 and Day 29 | NAI titers at D01 and D29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 to Day 29 | 2-fold and 4-fold increase in neutralizing titers D01 through D29 |
| Neutralizing antibodies titers | At Day 1 and Day 29 | Neutralizing antibodies titers at D01 and D29 |
Countries
Australia, United States
Outcome results
None listed