Simultaneous mRNA COVID-19 and IIV4 Vaccination Study

• ClinicalTrials.gov Identifier: NCT05028361
• Recruitment Status: Active, not recruiting
• First Posted: August 31, 2021
• Last Update Posted: March 16, 2023
• Sponsor: Duke University
• Collaborators: Centers for Disease Control and Prevention; Johns Hopkins University; Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: August 30, 2021
• First Posted Date: August 31, 2021
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: October 4, 2021
• Actual Primary Completion Date: February 23, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2021)

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 [ Time Frame: Visit 1 and Visit 2, Up to 7 Days Post Vaccination ]

Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 30, 2021)

• 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 [ Time Frame: Visit 1, Up to 7 Days Post Vaccination ]
  Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.
• Number of participants with moderate or more severe fever, chills, myalgia, or arthralgia in the Simultaneous versus Sequential Group following the second vaccination visit [ Time Frame: Visit 2, Up to 7 Days Post Vaccination ]
  Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.
• 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 [ Time Frame: Up to 7 Days Post Vaccination ]
  Subjects will be asked to complete a memory aid to document symptoms and measure temperature daily.
• Observed serious adverse events in both treatment groups [ Time Frame: Up to Day 121 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Simultaneous mRNA COVID-19 and IIV4 Vaccination Study
• Official Title: Safety of Simultaneous Versus Sequential Administration of mRNA COVID-19 Vaccines and Quadrivalent Inactivated Influenza Vaccine (IIV4) in Adults and Adolescents: A Randomized Observer Blinded Study
• Brief Summary: 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 vaccine either simultaneously or sequentially, 14 days apart. A second dose of mRNA COVID vaccine will be administered either 3 or 4 weeks following the first dose, depending upon the mRNA COVID vaccine received for participants receiving their initial dose of mRNA COVID vaccine. For those receiving a third dose of mRNA COVID vaccine, there will not be a second dose. Solicited symptoms of reactogenicity 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. Serum samples from participants will be collected for determination of COVID-19 seropositivity at baseline. Serum samples will be taken throughout the study to determine IIV4 immunogenicity and for potential future studies.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Pain
• Quality of Life
• Injection Site Reaction
• Adverse Drug Event

Intervention

• Biological: mRNA COVID-19
  ACIP recommended vaccine
• Biological: IIV4
  ACIP recommended vaccine
• Other: Placebo
  Saline Control

Study Arms

• 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 for participants receiving their primary series of mRNA COVID-19 vaccine.
  Interventions:

  • Biological: mRNA COVID-19
  • Biological: IIV4
  • Other: Placebo
• Sequential Vaccination Group
  Subjects will receive a dose of mRNA COVID-19 vaccine (either as a study procedure or standard of care) and placebo at Visit 1, IIV4 at Visit 2, and mRNA COVID-19 vaccine at Visit 3 for participants receiving their primary series of mRNA COVID-19 vaccine.
  Interventions:

  • Biological: mRNA COVID-19
  • Biological: IIV4
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 14, 2023): 349
• Original Estimated Enrollment (submitted: August 30, 2021): 450
• Estimated Study Completion Date: June 30, 2023
• Actual Primary Completion Date: February 23, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Persons aged ≥12 years if receiving primary two-dose mRNA COVID-19 vaccine series or persons aged ≥18 years if receiving a third 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
• 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 2021-2022 influenza season
• Prior receipt of non-mRNA COVID-19 vaccine
• Prior receipt of more than 2 mRNA COVID-19 vaccines
• 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 document 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

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05028361
• Other Study ID Numbers: Pro00109102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Duke University
• Original Responsible Party: Same as current
• Current Study Sponsor: Duke University
• Original Study Sponsor: Same as current

Collaborators

• Centers for Disease Control and Prevention
• Johns Hopkins University
• Children's Hospital Medical Center, Cincinnati

Investigators

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

• PRS Account: Duke University
• Verification Date: March 2023