Clinical trial NCT04969276: Study of a Quadrivalent High-Dose Influenza Vaccine and a Moderna COVID-19 Vaccine Administered Either Concomitantly or Singly in Participants 65 Years of Age and Older Previously Vaccinated With a 2-dose Schedule of Moderna COVID-19 Vaccine
Official title: A Phase II, Open-label Study to Assess the Safety and Immunogenicity of Fluzone® High-Dose Quadrivalent (Influenza Vaccine), 2021-2022 Formulation and a Third Dose of Moderna COVID-19 Vaccine (mRNA-1273 Vaccine) Administered Either Concomitantly or Singly in Adults 65 Years of Age and Older Previously Vaccinated With a 2-dose Schedule of Moderna COVID-19 Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza Immunization
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-07-20
Enrollment: 306
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main purpose of this Phase II study was to assess the safety and immunogenicity of a dose of Fluzone High-Dose (HD) Quadrivalent vaccine and a third dose or booster dose of Moderna coronavirus disease 19 (COVID-19) vaccine administered concomitantly or singly in adults 65 years of age and older having received their second dose of the 2-dose schedule of Moderna COVID-19 vaccine at least 5 months before enrollment in the study.

Detailed description: Participants were in the study for 6 months (approximately 180 days).

Eligibility criteria: Inclusion Criteria:

* Aged greater than or equal to \>= 65 years of age on the day of inclusion.
* In good health or with underlying medical condition(s) that were judged to be stable by the Investigator. A stable medical condition was defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.
* Participants who previously received 2 injections of Moderna COVID-19 Vaccine with the second dose received at least 5 months before Visit 1.
* Abled to attend all scheduled visits and to complied with all study procedures.

Exclusion Criteria:

* 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 3 months preceding planned inclusion).
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances.
* Previous dermal filler injection (either lips or face fillers).
* Thrombocytopenia, contraindicated IM injection.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicated IM vaccination.
* Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
* Moderate or severe acute illness/infection (according to Investigator judgment) on the day of study intervention administration or febrile illness (temperature \>= 100.4°Fahrenheit \[F\] \[38.0° Celsius {C}\]). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
* History of serious adverse reaction to any influenza or COVID-19 vaccines.
* Personal history of Guillain-Barré syndrome (GBS).
* Personal history of clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.
* Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.
* Any condition that in the opinion of the Investigator posed a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine.
* Receipt of any vaccine in the 4 weeks preceding the study intervention(s) administration or planned receipt of any vaccine in the period between Visit 01 and 4 weeks following the study intervention(s) administration. Note: Vaccination of Group 3 participants with Fluzone High-Dose Quadrivalent vaccine at the end of the study was not considered by the Sponsor as meeting this exclusion criterion.
* Receipt of blood-derived immune globulins, blood, or blood-derived products in the past 3 months.
* Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating vaccine, drug, medical device, or medical procedure.
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
* Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
* The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Immediate Unsolicited Adverse Events (AEs)
timeFrame: Within 30 minutes post vaccination
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Within 7 days post-vaccination
measure: Number of Participants With Solicited Systemic Reactions
timeFrame: Within 7 days post-vaccination
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Within 21 days post-vaccination
measure: Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs)
timeFrame: From Day 1 up to 6 months post-vaccination
measure: Number of Participants With Medically Attended Adverse Events (MAAEs)
timeFrame: From Day 1 up to 6 months post-vaccination
measure: Geometric Mean Titers (GMTs) of Influenza Vaccine and COVID-19 Vaccine Antibodies at Day 1
timeFrame: Day 1 (pre-vaccination)
measure: Geometric Mean Titers (GMTs) of Influenza Vaccine and COVID-19 Vaccine Antibodies at Day 22
timeFrame: Day 22 (post-vaccination)
measure: Geometric Mean Titers Ratio (GMTR) of Influenza Vaccine and COVID-19 Vaccine Antibodies
timeFrame: Day 1 (pre-vaccination) and Day 22 (post-vaccination)
measure: Percentage of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution)
timeFrame: Day 1 (pre-vaccination)
measure: Percentage of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution)
timeFrame: Day 22 (post-vaccination)
measure: Percentage of Participants Achieving Seroconversion Against Influenza and COVID-19 Virus Antigens
timeFrame: Day 22 (post-vaccination)
measure: Percentage of Participants With Antibody Titers >=40 (1/Dilution)
timeFrame: Day 1 (pre-vaccination)
measure: Percentage of Participants With Antibody Titers >=40 (1/Dilution)
timeFrame: Day 22 (post-vaccination)
measure: Geometric Mean Concentration (GMC) of Anti-S Binding Immunoglobulin G (IgG) Antibodies
timeFrame: Day 1 (pre-vaccination)
measure: Geometric Mean Concentration (GMC) of Anti-S Binding Immunoglobulin G (IgG) Antibodies
timeFrame: Day 22 (post-vaccination)
measure: Geometric Mean Concentration Ratio (GMCR) of Anti-S Binding IgG Antibodies
timeFrame: Day 1 (pre-vaccination) and Day 22 (post-vaccination)
measure: Percentage of Participants With >=2-Fold and >=4-Fold Rise in Anti-S Binding IgG Antibodies
timeFrame: Day 22 (post-vaccination)
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Investigational Site Number :8400003
state: Arizona
city: San Diego
country: United States
facility: Investigational Site Number :8400006
state: California
city: Vista
country: United States
facility: Investigational Site Number :8400004
state: California
city: Centennial
country: United States
facility: Investigational Site Number :8400005
state: Colorado
city: Peoria
country: United States
facility: Investigational Site Number :8400001
state: Illinois
city: Austin
country: United States
facility: Investigational Site Number :8400002
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Izikson R, Brune D, Bolduc JS, Bourron P, Fournier M, Moore TM, Pandey A, Perez L, Sater N, Shrestha A, Wague S, Samson SI. Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged >/=65 years: a phase 2, randomised, open-label study. Lancet Respir Med. 2022 Apr;10(4):392-402. doi: 10.1016/S2213-2600(21)00557-9. Epub 2022 Feb 1.