Simultaneous mRNA COVID-19 and IIV4 Vaccination Study

Safety of Simultaneous Versus Sequential Administration of mRNA COVID-19 Vaccines and Quadrivalent Inactivated Influenza (IIV4) in Adults, Adolescents and Children: A Randomized Observer Blinded Study

This study is a prospective, randomized clinical trial. During this study, participants will be randomly assigned to receive quadrivalent inactivated influenza vaccine (IIV4) and mRNA COVID-19 vaccine either simultaneously or sequentially, 7-14 days apart. Persons in the simultaneous group will receive mRNA COVID-19 and IIV4 at Visit 1 (Day 1) and a saline placebo injection at Visit 2. Persons in the sequential group will receive mRNA COVID-19 vaccine and a saline placebo at Visit 1 (Day 1) and IIV4 injection at Visit 2. For participants receiving their primary dose series, a second dose of mRNA COVID-19 vaccine will be administered either 3 to 8 weeks or 4 to 8 weeks following the first dose, depending upon the mRNA COVID-19 vaccine provided. For those receiving a booster dose of mRNA COVID-19 only a single mRNA COVID-19 will be received in this study. Solicited symptoms of reactogenicity and adverse events will be assessed on vaccination day and daily during the 7 days following each Vaccination Visit using either electronic or paper symptoms diaries, depending on study participant preference. Quality of life data will be collected using electronic or paper diaries on day of Vaccination Visit 1 and daily during the 7 days following the visit. Serious adverse events and adverse events of special interest will be collected throughout the duration of the study. Participants are followed through Day 121. Serum samples from participants will be collected for determination of SARS-CoV-2 seropositivity at baseline. Serum samples will be taken throughout the study to determine IIV4 and COVID-19 vaccine immunogenicity and for potential future studies.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Adverse Drug Event; Injection Site Reaction; Systemic Reaction
• Intervention / Treatment: Biological: IIV4; Biological: mRNA COVID-19; Other: Placebo (saline)

• Study Type: Interventional
• Enrollment (Actual): 348
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Emmanual B Walter, MD, MPH; Phone Number: 919-620-5346; Email: chip.walter@duke.edu
• Study Contact Backup: Name: Grace N Davis, MS; Phone Number: 919-385-5786; Email: grace.davis@duke.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • John Hopkins University
  • North Carolina
    • Durham, North Carolina, United States, 27709
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Persons aged ≥5 years if receiving primary two-dose mRNA COVID-19 vaccine series or persons aged ≥12 years if receiving a booster mRNA COVID-19 vaccine dose according to FDA authorization or approval and ACIP recommendation. Note: receipt of an mRNA COVID-19 vaccine within 8 hours of enrollment is permitted

  *Individuals age 5-11 receiving a booster may be enrolled in the event a booster for individuals age 5-11 is authorized or approved and recommended by the ACIP.

• English or Spanish literate
• Intention of receiving influenza vaccine and COVID-19 vaccine based on ACIP-CDC guidelines
• Willing to provide written informed consent
• Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and clinic visits

Exclusion Criteria:

• 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 as defined in Section 5.1 at Visit 1
• Prior receipt of IIV4 during the respective influenza season in which they 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
• Prior receipt of non-mRNA COVID-19 vaccine
• Documented COVID-19 infection within 6 weeks prior to enrollment confirmed by either medical history or lab testing
• History of severe allergic reaction after a previous dose of any influenza vaccine; or to an influenza vaccine component, including egg protein
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of an mRNA vaccine
• Receipt of any licensed inactivated vaccine within 2 weeks prior to enrollment in this study, receipt of any licensed live vaccine within 4 weeks prior to enrollment in this study, or receipt of Shingrix (Zoster Vaccine Recombinant, Adjuvanted) or HEPLISAV-B (Hepatitis B Vaccine (Recombinant), Adjuvanted) vaccine within 6 weeks prior to enrollment in this study or planning receipt of any vaccines following enrollment until 6 weeks after receipt of the second dose of mRNA COVID-19 vaccine
• Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy* *Participants with a history of malignancy may be included if, after previous treatment by surgical excision, chemotherapy or radiation therapy, the participant has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure
• Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection (a daily aspirin may be acceptable).

• Has immunosuppression as a result of an underlying illness or medications, such as antirejection/transplant regimens or immunomodulatory agents. Stable HIV disease is permitted per the following parameters:

  a. Confirmed stable HIV disease defined as documented viral load <50 copies/mL and CD4 count >200 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months

• Has known hepatitis B (HBV) or hepatitis C (HBC). Stable HBV or HBC are permitted per the following parameters:

  1. If known HBV: confirmed inactive chronic HBV infection: HBsAg present for ≥6 months and HBeAg negative, anti-HBe positive; serum HBV DNA <2000 IU/mL; persistently normal ALT or AST levels; in those who had liver biopsy, findings that confirm absence of significant necroinflammation
  2. If known HCV: evidence of sustained virological response for ≥12 weeks after treatment or without evidence of HCV RNA viremia (undetectable HCV RNA)

• Use of oral, parenteral, or high-dose inhaled glucocorticoids*

  *For definition of high-dose inhaled glucocorticoids, reference Appendix B.

• History of Guillain-Barré syndrome
• Prior enrollment in this study during the 2021-22 flu season

• Anyone who is already enrolled or plans to enroll in another clinical trial with an investigational product during the study period.*

  *Per protocol, co-enrollment in observational or behavioral intervention studies are permitted at any time. An investigational product may be permitted for therapy of an illness condition that occurs during the study period e.g. COVID-19 illness.

• Hearing loss determined by the investigators to prevent successful communication over the phone
• History of myocarditis or pericarditis
• History of multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A).
• 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 subject or interfere with the evaluation of the study objectives.
• Anyone who is a relative of any research study personnel.
• Anyone who is an employee of any research study personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Simultaneous Vaccination Group; Subjects will receive a dose of mRNA COVID-19 vaccine (either as a study procedure or standard of care) and IIV4 at Visit 1, saline placebo at Visit 2, and mRNA COVID-19 vaccine at Visit 3 (only for participants receiving their primary series of mRNA COVID-19 vaccine.)	Biological: IIV4; ACIP recommended vaccine; Biological: mRNA COVID-19; ACIP-CDC recommended vaccine; Other: Placebo (saline); Saline Control
Other: Sequential Vaccination Group; Subjects will receive a dose of mRNA COVID-19 vaccine (either as a study procedure or standard of care) and saline placebo at Visit 1, IIV4 at Visit 2, and mRNA COVID-19 vaccine at Visit 3 (only for participants receiving their primary series of mRNA COVID-19 vaccine.)	Biological: IIV4; ACIP recommended vaccine; Biological: mRNA COVID-19; ACIP-CDC recommended vaccine; Other: Placebo (saline); Saline Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Participants With Moderate or More Severe Fever, Chills, Myalgia, or Arthralgia in the Simultaneous Group and the Sequential Group Following Both Vaccination Visit 1 and 2	Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.	Up to 7 Days Post Vaccination (combined for Visits 1 and 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Moderate or More Severe Fever, Chills, Myalgia, or Arthralgia in the Simultaneous Versus the Sequential Group Following the First Vaccination Visit	Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.	Up to 7 Days Post Vaccination
Number of Participants With Moderate or More Severe Fever, Chills, Myalgia, or Arthralgia in the Simultaneous Versus Sequential Group Following the Second Vaccination Visit	Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.	Up to 7 Days Post Vaccination
Number of Participants in the Simultaneous and Sequential Vaccination Groups With Solicited Local and Systemic Reactogenicity Events According to Severity Grade After the First, Second and Third Vaccination Visit	Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.	Up to 7 Days Post Vaccination
Number of Participants With Observed Serious Adverse Events		120 Days

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Johns Hopkins University; Centers for Disease Control and Prevention; Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Kawsar Talaat, MD, Johns Hopkins University; Principal Investigator: Emmanuel B Walter, MD, MPH, Duke University; Principal Investigator: Elizabeth Schlaudecker, MD, MPH, Children's Hospital Medical Center, Cincinnati; Principal Investigator: Karen R Broder, MD, Centers for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: safety; quality of life; vaccine; Influenza; COVID-19; influenza vaccine; fever following vaccination; pain following vaccination; mRNA COVID-19 vaccine
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Extravasation of Diagnostic and Therapeutic Materials; COVID-19; Drug-Related Side Effects and Adverse Reactions; Injection Site Reaction
• Other Study ID Numbers: Pro00109102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes