Clinical trial NCT06020118: Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations
Official title: Randomized Study of the Immunogenicity and Duration of Antibody Response Against Circulating SARS-CoV-2 Variant and Influenza Viruses Following Concomitant Versus Sequential Administration of mRNA COVID-19 Vaccine and Quadrivalent Cell Culture-based Influenza Vaccine Among Children and Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
COVID-19
Keywords: Influenza
COVID-19
Immunogencity
Health
Reactogenicity
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: Arizona State University
name: University Hospitals Cleveland Medical Center
name: University of Pittsburgh
name: Washington University School of Medicine
name: Valleywise Health
name: Cleveland VA Medical Center
name: Senders Pediatrics
First posted: 2023-08-31
Enrollment: 455
Sex: ALL
Minimum age (years): 6
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a prospective, randomized randomized immunologic study of response to influenza and SARS-CoV-2 vaccination across four of the US Influenza Vaccine Effectiveness (Flu VE) Network study sites.

Detailed description: This study is a prospective, randomized comparative immunogenicity study in an enrolled cohort. During this study, eligible participants will be randomly assigned to receive an approved quadrivalent cell culture-based influenza vaccine (ccIIV4, Seqirus) and an approved mRNA COVID-19 vaccine (Moderna) either concomitantly or sequentially, 28 days apart. Participants (aged 6-11 years and 18-64 years) will be enrolled in the 2023-2024 influenza season.

Demographic and health data (including influenza and COVID-19 vaccination and infection history) will be collected upon enrollment. Enrolled participants will be randomized to one of the following interventions (2:1:1) (i) concomitant administration of the mRNA COVID-19 vaccine (Moderna) and quadrivalent influenza vaccine (ccIIV4, Seqirus); (ii)sequential administration of the quadrivalent influenza vaccine (ccIIV4, Seqirus) at Visit 1 (day 0) and the mRNA COVID-19 vaccine(Moderna) at Visit 2 (day 28); (iii) sequential administration of the mRNA COVID-19 vaccine (Moderna) at Visit 1 (day 0) followed by the quadrivalent influenza vaccine (ccIIV4, Seqirus) at Visit 2 (day 28). Participants will not be blinded to vaccine group.

Whole blood samples to isolate sera for immune assays will be collected prior to vaccination administration at Visit 1 (day 0), Visit 2 (day 28) Visit 3 (day 56; post-vaccination 2) and Visit 4 (day180; end of local flu circulation). Blood samples to isolate PBMC and plasma will be collected from a subset of 250 participants (200 adults and 50 children). If participants exhibit ARI during the study period, the participants may be asked to present for collection of a nasal swab for viral testing for acute influenza or SARS-CoV-2 infection (within 10 days after symptom onset), and blood specimen to isolate sera for immune assays. For participants with confirmed acute infection, the participants may be asked to present for collection of a convalescent-phase blood specimen approximately 28 days after acute visit for isolation of sera, PBMC and plasma.

Eligibility criteria: Inclusion Criteria:

* Healthy children aged 6-11 years and healthy adults aged 18-64 years that have not received the current season's influenza vaccination or a mRNA COVID-19 vaccination in the past 6 months and have already completed at least a two-dose primary series of an mRNA COVID-19 vaccination
* English or Spanish literate
* Email or text message capability for weekly follow-up
* Intention of receiving influenza vaccine and mRNA COVID-19 vaccine based on ACIP-CDC guidelines
* Willing to provide written/electronic informed consent
* Intention of being available for entire study period and able to complete all relevant study procedures, including follow-up phone calls and clinic visits

Exclusion Criteria:

* Self-reported COVID-19 infection within 3 months prior to enrollment
* Received COVID-19 vaccine within 6 months prior to enrollment
* Received influenza vaccine during the respective influenza season in which the participants are being enrolled
* \< 9 years of age and recommended to receive two doses of IIV4 during the respective influenza season in which they are being enrolled
* History of severe allergic reaction after a previous dose of any influenza or COVID-19 mRNA vaccine; or to an influenza or COVID-19 mRNA vaccine component
* Receipt of any licensed vaccine within 6 weeks prior to enrollment in this study or planning receipt of any vaccines within 4 weeks after the receipt of the second vaccine dose administered during study procedures
* Has an immunocompromising condition or taking immunosuppressive medication\*

  \* Received oral, intramuscular or intravenous systemic immunosuppressants, or immune modifying drugs for \>14 days in total within 6 months prior to any study vaccine dose (for corticosteroids ≥ 20 mg/day of prednisone equivalent).

  \*\* Note: Topical medications are allowed
* Received immunoglobulin, SARS-CoV-2 immunoglobulin, SARS-CoV-2 monoclonal antibody, or blood-derived products, within 3 months prior any study vaccine dose.
* History of Guillain-Barré syndrome
* History of myocarditis or pericarditis
* History of multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A)
* Currently pregnant, planning to become pregnant within the first three months of the study per participant self-report or likely to be pregnant per screening criteria
* Bleeding disorder diagnosed by a healthcare provider or bleeding difficulties with intramuscular injections or blood draws.
* Has injury or other reason why deltoid site on both arms cannot be used for vaccinations
* Any condition which, in the opinion of the investigators, may pose a health risk to the participant or interfere with the evaluation of the study objectives
* Temporary Delay Criteria: History of febrile illness (\> 100.0°F or 37.8°C) within the past 72 hours prior to vaccine administration

Primary outcomes:
measure: Percentage of Participants With HAI Seroconversion
timeFrame: Visit 1 (day 1; baseline) to Visit 2 (days 28-42; post-vaccination) for all arms/groups
measure: Percentage of Participants With HAI Seroprotection
timeFrame: Visit 1 (day 1; baseline; pre-immunization) and Visit 2 (days 28-42; post-immunization) for all arms/groups
measure: HAI Geometric Mean Titer
timeFrame: Visit 1 (day 1; baseline; pre-immunization) and Visit 2 (days 28-42; post-immunization) for all arms/groups
measure: HAI Geometric Mean Fold Rise (GMFR)
timeFrame: Visit 1 (day 1; baseline) to Visit 2 (days 28-42; post-vaccination) for all arms/groups
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Valleywise Health Comprehensive Health Center
state: Arizona
city: Tempe
country: United States
facility: ASU Biodesign Institute
state: Arizona
city: Atlanta
country: United States
facility: Centers for Disease Control and Prevention
state: Georgia
city: Saint Louis
country: United States
facility: Washington University IDCRU
state: Missouri
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: VA Northeast Ohio Healthcare System (VANEOHS)
state: Ohio
city: South Euclid
country: United States
facility: Senders Pediatrics
state: Ohio
city: Pittsburgh
country: United States
facility: Department of Family Medicine, University of Pittsburgh School of Medicine
state: Pennsylvania
Study officials:
References: