Clinical trial NCT06744205: A Study on the Safety and Immunogenicity of Hexavalent Influenza mRNA Vaccine in Adult Participants 50 Years of Age and Older
Official title: A Phase I/II, Randomized, Modified Double-blind Study to Investigate the Safety and Immunogenicity of Different Doses of Hexavalent Influenza mRNA HA + mRNA NA Vaccine in Adult Participants 50 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Influenza
Healthy Volunteers
Keywords: influenza, flu, vaccine, hexavalent
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-12-20
Enrollment: 1162
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort.
Primary purpose: PREVENTION

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with immediate unsolicited systemic adverse events (AEs)
timeFrame: Within 30 minutes after injection
measure: Number of participants with solicited injection site reactions
timeFrame: Up to 7 days after injection
measure: Number of participants with solicited systemic reactions
timeFrame: Up to 7 days after injection
measure: Number of participants with unsolicited AEs
timeFrame: Up to 28 days after injection
measure: Number of participants with medically attended adverse events (MAAEs)
timeFrame: Up to 180 days after injection
measure: Number of participants with serious adverse events (SAEs)
timeFrame: SAEs throughout the study (Up to approximately 12 months)
measure: Number of participants with adverse events of special interest (AESIs)
timeFrame: AESIs throughout the study (Up to approximately 12 months)
measure: Number of participants with out-of-range biological test results
timeFrame: Up to 8 days after injection
measure: Hemagglutinin inhibition (HAI) titers
timeFrame: At Day 1 and Day 29
measure: Individual HAI antibody (Ab) titer ratio D29/D01
timeFrame: At Day 1 and Day 29
measure: Seroconversion (HAI Ab titer)
timeFrame: At Day 1 and Day 29
measure: HAI Ab titer ≥ 40 (1/dil)
timeFrame: At Day 29
measure: Neuraminidase inhibition (NAI) titers
timeFrame: At Day 1 and Day 29
measure: Individual NAI Ab titer ratio D29/D01
timeFrame: At Day 1 and Day 29
measure: Seroconversion (NAI Ab titer)
timeFrame: At Day 1 and Day 29
measure: NAI Ab titer ≥ 40 (1/dil)
timeFrame: At Day 29
measure: 2-fold and 4-fold rise in NAI titers
timeFrame: Day 1 to Day 29
Secondary outcomes:
measure: Neutralizing antibodies titers
timeFrame: At Day 1 and Day 29
measure: Individual neutralizing antibodies titer ratio
timeFrame: At Day 1 and Day 29
measure: 2-fold and 4-fold increase in neutralizing titers
timeFrame: Day 1 to Day 29
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research Sites Network - Birmingham- Site Number : 8400008
state: Alabama
city: Mobile
country: United States
facility: AMR Mobile- Site Number : 8400022
state: Alabama
city: Tempe
country: United States
facility: Alliance for Multispeciality Research - Clinical Research Consortium- Site Number : 8400015
state: Arizona
city: Coral Gables
country: United States
facility: AMR Miami- Site Number : 8400021
state: Florida
city: DeLand
country: United States
facility: Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400003
state: Florida
city: Fort Myers
country: United States
facility: Alliance for Multispeciality Research - Fort Myers- Site Number : 8400013
state: Florida
city: Maitland
country: United States
facility: Accel Research Sites - Maitland- Site Number : 8400007
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center - Palmetto Bay- Site Number : 8400011
state: Florida
city: Decatur
country: United States
facility: Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400001
state: Georgia
city: Oak Brook
country: United States
facility: AMR - Chicago- Site Number : 8400012
state: Illinois
city: Newton
country: United States
facility: Alliance for Multispeciality Research - Newton- Site Number : 8400020
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispeciality Research - Wichita East- Site Number : 8400014
state: Kansas
city: Lexington
country: United States
facility: Alliance for Multispeciality Research - Lexington- Site Number : 8400018
state: Kentucky
city: Boston
country: United States
facility: Boston Clinical Trials- Site Number : 8400009
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices & Research- Site Number : 8400005
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute- Site Number : 8400010
state: Michigan
city: Kansas City
country: United States
facility: Alliance for Multispeciality Research - Kansas City- Site Number : 8400019
state: Missouri
city: Las Vegas
country: United States
facility: AMR Las Vegas - Site Number : 8400016
state: Nevada
city: North Charleston
country: United States
facility: Coastal Carolina Research Center - North Charleston- Site Number : 8400002
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispeciality Research - Knoxville- Site Number : 8400017
state: Tennessee
city: Charlottesville
country: United States
facility: Charlottesville Medical Research- Site Number : 8400004
state: Virginia
city: Botany
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Bayswater
country: Australia
facility: Investigational Site Number : 0360003
state: Victoria
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360002
state: Victoria
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: