Simultaneous mRNA COVID-19 and IIV4 Vaccination Study

NCT05028361 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: Pro00109102
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 3

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

Keywords

COVID-19; Influenza; vaccine; mRNA COVID-19 vaccine; influenza vaccine; safety; quality of life; pain following vaccination; fever following vaccination

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  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

  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

  Up to 7 Days Post Vaccination

• Number of Participants With Observed Serious Adverse Events

  120 Days

Study Arms (2)

Simultaneous Vaccination Group

OTHER

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: mRNA COVID-19; Biological: IIV4; Other: Placebo (saline)

Sequential Vaccination Group

OTHER

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: mRNA COVID-19; Biological: IIV4; Other: Placebo (saline)

Interventions

mRNA COVID-19 BIOLOGICAL

ACIP-CDC recommended vaccine

Sequential Vaccination Group; Simultaneous Vaccination Group

IIV4 BIOLOGICAL

ACIP recommended vaccine

Sequential Vaccination Group; Simultaneous Vaccination Group

Placebo (saline) OTHER

Saline Control

Sequential Vaccination Group; Simultaneous Vaccination Group

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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
• If known HCV: evidence of sustained virological response for ≥12 weeks after treatment or without evidence of HCV RNA viremia (undetectable HCV RNA)

Sponsors & Collaborators

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

Study Sites (3)

John Hopkins University

Baltimore, Maryland, 21205, United States

Location

Duke University

Durham, North Carolina, 27709, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (2)

• Walter EB, Schlaudecker EP, Talaat KR, Rountree W, Broder KR, Duffy J, Montefiori D, Poniewierski MS, Spreng RL, Staat MA, Tekalign R, Museru O, Goel A, Davis GN, Schmader KE. Immunogenicity of mRNA COVID-19 vaccine with either simultaneous or sequentially administered inactivated influenza vaccines: a randomized clinical trial. Vaccine. 2026 Feb 6;72:128072. doi: 10.1016/j.vaccine.2025.128072. Epub 2025 Dec 10.

  PMID: 41380398 DERIVED

• 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.

  PMID: 39504023 DERIVED

MeSH Terms

Conditions

Injection Site Reaction; Drug-Related Side Effects and Adverse Reactions; COVID-19; Influenza, Human

Interventions

2019-nCoV Vaccine mRNA-1273; Sodium Chloride

Condition Hierarchy (Ancestors)

Extravasation of Diagnostic and Therapeutic Materials; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Orthomyxoviridae Infections

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Emmanuel Walter
• Organization: Duke Human Vaccine Institute

chip.walter@duke.edu

919 620 5346

Study Officials

• Emmanuel 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: August 31, 2021
• Study Start: October 4, 2021
• Primary Completion: March 3, 2023
• Study Completion: June 15, 2023
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)