Clinical trial NCT06361875: A Study to Investigate the Safety and Immunogenicity of the Quadrivalent Influenza mRNA Vaccines in Adults Aged 18 Years and Above
Official title: A Phase I/II Study to Investigate the Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccines MRT5421, MRT5424, and MRT5429 in Healthy Participants Aged 18 Years and Above
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Influenza Immunization
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-04-12
Enrollment: 910
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel with dose escalation for sentinel cohort
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

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: Throughout the study (approximately 12 months)
measure: AESIs reported throughout the study
timeFrame: AESIs reported throughout the study (approximatley 12 months)
measure: Number of participants with adverse events of special interests (AESIs)
timeFrame: Throughout the study (approximately 12 months)
measure: Number of participants with out-of-range biological test results
timeFrame: Up to 8 days after injection
measure: Geometric Mean Titer (GMT)
timeFrame: At Day 1 and Day 29
measure: Geometric Mean of individual Titer Ratio (GMTR)
timeFrame: At Day 1 and Day 29
measure: Seroconversion
timeFrame: At Day 1 and Day 29
measure: HAI Ab titer ≥ 40 (1/dil)
timeFrame: Day 29
Secondary outcomes:
measure: Neutralizing Ab titers at D01 and D29
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 through Day 29
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Clinical Trials Site Number : 8400013
state: California
city: San Diego
country: United States
facility: California Research Foundation Site Number : 8400038
state: California
city: DeLand
country: United States
facility: Accel Clinical Research-Deland Clinical Research Unit Site Number : 8400001
state: Florida
city: Gainesville
country: United States
facility: SIMEDHealth, LLC Site Number : 8400011
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center Site Number : 8400032
state: Florida
city: Hollywood
country: United States
facility: Cenexel Research Centers of America Site Number : 8400037
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC Site Number : 8400015
state: Florida
city: Indianapolis
country: United States
facility: Brengle Family Medicine Site Number : 8400045
state: Indiana
city: Lexington
country: United States
facility: AMR Lexington Site Number : 8400042
state: Kentucky
city: New Orleans
country: United States
facility: Velocity Clinical Research- New Orleans Site Number : 8400053
state: Louisiana
city: Kansas City
country: United States
facility: The Alliance for Multispecialty Research - KCM, LLC Site Number : 8400034
state: Missouri
city: Norfolk
country: United States
facility: Velocity Clinical Research Norfolk Site Number : 8400046
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha Site Number : 8400008
state: Nebraska
city: Rochester
country: United States
facility: Rochester Clinical Research. Inc. Site Number : 8400005
state: New York
city: North Charleston
country: United States
facility: Coastal Carolina Research Center Site Number : 8400014
state: South Carolina
city: Knoxville
country: United States
facility: AMR Knoxville Site Number : 8400043
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc. - PPDS Site Number : 8400029
state: Texas
city: Salt Lake City
country: United States
facility: Cenexel JBR Site Number : 8400051
state: Utah
city: San Pedro Sula
country: Honduras
facility: Investigational Site Number : 3400001
city: Barrio Sabana
country: Puerto Rico
facility: Investigational Site Number : 6300002
Study officials:
References: