Simultaneous mRNA COVID-19 and IIV4 Vaccination Study

NCT ID: NCT05028361

Last Updated: 2024-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 348 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-04
• Study Completion Date: 2023-06-15

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-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.

Conditions

Quality of Life; Injection Site Reaction; Adverse Drug Event; Systemic Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.)

Group Type: OTHER

mRNA COVID-19

Intervention Type: BIOLOGICAL

ACIP-CDC recommended vaccine

IIV4

Intervention Type: BIOLOGICAL

ACIP recommended vaccine

Placebo (saline)

Intervention Type: OTHER

Saline Control

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.)

Group Type: OTHER

mRNA COVID-19

Intervention Type: BIOLOGICAL

ACIP-CDC recommended vaccine

IIV4

Intervention Type: BIOLOGICAL

ACIP recommended vaccine

Placebo (saline)

Intervention Type: OTHER

Saline Control

Interventions

mRNA COVID-19

ACIP-CDC recommended vaccine

Intervention Type: BIOLOGICAL

IIV4

ACIP recommended vaccine

Intervention Type: BIOLOGICAL

Placebo (saline)

Saline Control

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel B Walter, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Duke University

Karen R Broder, MD

Role: PRINCIPAL_INVESTIGATOR

Centers for Disease Control and Prevention

Kawsar Talaat, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Elizabeth Schlaudecker, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

John Hopkins University

Baltimore, Maryland, United States

Duke University

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

References

Walter EB, Schlaudecker EP, Talaat KR, Rountree W, Broder KR, Duffy J, Grohskopf LA, Poniewierski MS, Spreng RL, Staat MA, Tekalign R, Museru O, Goel A, Davis GN, Schmader KE. Safety of Simultaneous vs Sequential mRNA COVID-19 and Inactivated Influenza Vaccines: A Randomized Clinical Trial. JAMA Netw Open. 2024 Nov 4;7(11):e2443166. doi: 10.1001/jamanetworkopen.2024.43166.

Reference Type: DERIVED

PMID: 39504023 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Pro00109102

Identifier Type: -

Identifier Source: org_study_id