Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children

A Prospective, Randomized, Open-label Clinical Trial to Assess the Safety of Simultaneous Vaccination With mRNA COVID-19 Vaccine and Other Vaccines in Young Children Aged 6 Months to <5 Years.

This is a prospective, randomized, open-label clinical trial to evaluate the safety of COVID-19 vaccination and other routine childhood vaccines given simultaneously at Visit 1, as compared to sequential vaccination of COVID-19 vaccine and other vaccines at separate visits (Visits 1 and 2).

Study Overview

• Status: Recruiting
• Conditions: Fever; Fever After Vaccination; Seizures Fever
• Intervention / Treatment: Biological: Routine Childhood Vaccinations; Biological: mRNA COVID-19 Vaccine

Detailed Description

Parent(s) or legal authorized representative(s) (LAR) will assess fever and other solicited systemic adverse events on the day of vaccination (Day 1) and the next 6 days (through Day 7) following Visit 1 and Visit 2 using either a web-based data collection system or a paper memory aid. Serious adverse events and adverse events of special interest will be captured during the entire study period. Parental/LAR perceptions about their child's vaccine schedule will be assessed on Day 7 following Visit 2.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michael J Smith, MD; Phone Number: 919-684-6335; Email: michael.j.smith@duke.edu
• Study Contact Backup: Name: Emily A Randolph, MBA; Phone Number: 919-353-5785; Email: emily.randolph@duke.edu

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Not yet recruiting
      • Kaiser Permanente Northern California
      • Contact: Nicola Klein, MD; Phone Number: 510-267-7540; Email: nicola.klein@kp.org
  • Georgia
    • Atlanta, Georgia, United States, 30333
      • Active, not recruiting
      • Centers for Disease Control and Prevention
  • New York
    • New York, New York, United States, 10027
      • Not yet recruiting
      • Columbia University
      • Contact: Melissa Stockwell, MD; Phone Number: 212-342-5732; Email: mss2112@cumc.columbia.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Contact: Michael J Smith, MD; Phone Number: 919-684-6335; Email: michael.j.smith@duke.edu
      • Contact: Emily A Randolph, MBA; Phone Number: 919-385-5785; Email: emily.randolph@duke.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Not yet recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Elizabeth Schlaudecker, MD; Phone Number: 513-803-0747; Email: elizabeth.schlaudecker@ccmc.org
      • Contact: Mary Staat, MD; Phone Number: 513-636-2877; Email: mary.staat@cchmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Child 6 months through <5 years of age at time of enrollment.
• Child is due to receive mRNA COVID-19 vaccine and at least one other routinely recommended non-live vaccine per CDC or ACIP recommendations.
• Parental/LAR intention of child receiving mRNA COVID-19 vaccine and at least one recommended non-live vaccine.
• The parent/LAR must be willing and capable of providing permission for their child to participate through the written informed consent process.
• The parent/LAR must be available for follow-up and must at minimum have telephone access.
• The parent/LAR must agree to sign a medical release for the child so that study personnel may obtain medical information about the child's health (if needed).
• The parent/LAR must be willing to delay COVID-19 vaccination for their child for up to 3 weeks.
• The parent/LAR must be able to read English or Spanish.

Exclusion Criteria:

• History of any seizure (including febrile seizure) or first degree relative (biologic parent or biologic sibling including half-sibling) with a history of febrile seizure.
• Contraindication to mRNA COVID-19 vaccine: A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of the COVID-19 vaccine or a known diagnosed allergy to a component of COVID-19 vaccine.
• A history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a vaccine administered on the day of study enrollment.
• For children receiving DTaP vaccine (alone or combination vaccine): Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of previous dose of DTP or DTaP.
• Received any other non-live vaccines within 14 days prior to enrollment or any other live vaccines within 28 days prior to enrollment.
• Intention to receive non-COVID-19 non-live or live vaccines during the 4 weeks after Visit 1; vaccines may be administered after enrollment if deemed a personal or public health priority by the health care provider caring for this patient or the study team.
• Received prior COVID-19 vaccine as part of a clinical trial.
• Received any experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to enrollment in this study or expects to receive an experimental/investigational agent during the study.
• A moderate to severe acute illness and/or a reported temperature ≥ 100.4°F (≥38.0°C) within 48 hours prior to enrollment or a temperature (measured by temporal artery thermometer) ≥100.4°F (≥38.0°C) at the time of enrollment. (This may result in a temporary delay of vaccination).
• Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours prior to enrollment (this may result in a temporary delay of vaccination) or planned receipt of a prophylactic antipyretic medication on the day of and/or days following vaccination prior to any measured increase in temperature in anticipation of a fever (this exclusion does not apply if the Parent/LAR indicates they might administer antipyretics or analgesics after vaccination to reduce a fever or pain).
• Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy since birth.
• Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other glucocorticoid) use of any parenteral steroids or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the 6 months prior to enrollment (topical and nasal steroids are allowed).
• Has an active case of COVID-19 infection.
• History of multisystem inflammatory syndrome (MIS-C).
• History of myocarditis or pericarditis.
• Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
• Any child or grandchild of a study investigator or study team member.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simultaneous vaccination arm; The simultaneous vaccination group will receive routine childhood vaccinations and mRNA COVID-19 vaccination at Visit 1, followed by a health education visit without vaccination at Visit 2.	Biological: Routine Childhood Vaccinations; ACIP Recommended Vaccines; Other Names: Pneumococcal, DTaP, Haemophilus Influenzae Type B, MMR, Varicella, MMRV, Hepatitis A, Inactivated Poliovirus, Hepatitis B, Rotavirus, Influenza vaccines; Biological: mRNA COVID-19 Vaccine; ACIP Recommended Vaccine; Other Names: Pfizer COVID-19 Vaccine, Moderna COVID-19 Vaccine
Experimental: Sequential vaccination arm; The sequential vaccination group will receive routine childhood vaccinations at Visit 1, followed by a health education visit with mRNA COVID-19 vaccination at Visit 2.	Biological: Routine Childhood Vaccinations; ACIP Recommended Vaccines; Other Names: Pneumococcal, DTaP, Haemophilus Influenzae Type B, MMR, Varicella, MMRV, Hepatitis A, Inactivated Poliovirus, Hepatitis B, Rotavirus, Influenza vaccines; Biological: mRNA COVID-19 Vaccine; ACIP Recommended Vaccine; Other Names: Pfizer COVID-19 Vaccine, Moderna COVID-19 Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Fever Following Vaccination	Number of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and/or Visit 2.	2 Days Post-Administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Fever Following Visit 1	Number of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1	2 Days Post Administration
Number of Participants with Fever Following Visit 2	Number of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2	2 Days Post Administration
Number of Participants with Grade 2 and/or 3 Fever Following Visit 1	Number of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)	2 Days Post Administration
Number of Participants with Grade 2 and/or 3 Fever Following Visit 2	Number of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)	2 Days Post Administration
Number of Participants with Grade 2 and/or 3 Fever Following Visit 1 and Visit 2 Combined	Number of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1 and Visit 2 combined. (Moderate/severe fever: ≥ 38.4°C or ≥ 101.2°F)	2 Days Post Administration
Number of Participants with Medical Care Utilization - Visit 1	Number of children with medical care utilization (medical advice (telephone, patient portal),urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and/or day 2 following Visit 1.	2 Days Post Administration
Number of Participants with Medical Care Utilization - Visit 2	Number of children with medical care utilization (medical advice (telephone, patient portal),urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and/or day 2 following Visit 2.	2 Days Post Administration
Number of Participants with Medical Care Utilization - Visit 1 and Visit 2 Combined	Number of children with medical care utilization (medical advice (telephone, patient portal), urgent care visit, emergency department visit, and hospital admission) for fever on day 1 and /or day 2 following Visit 1 and Visit 2 combined.	2 Days Post Administration
Number of Participants who Received Antipyretics - Visit 1	Number of children who received antipyretics on day 1 and/or day 2 following Visit 1.	2 Days Post Administration
Number of Participants who Received Antipyretics - Visit 2	Number of children who received antipyretics on day 1 and/or day 2 following Visit 2.	2 Days Post Administration
Number of Participants who Received Antipyretics - Visit 1 and Visit 2 Combined	Number of children who received antipyretics on day 1 and/or day 2 following Visit 1 and Visit 2 combined.	2 Days Post Administration
Number of Participants with Defined Systemic Reactogenicity Events	Tables summarizing each solicited local and systemic reactogenicity event by maximum classification (none, mild, moderate, and severe), as well as by moderate or severe	Up to 7 Days Post Administration
The Number and Percent of Individuals with At Least One Serious Adverse Event	The number and percent of serious adverse events observed and description of each event	Up to 105 Days Post Administration

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Columbia University; Centers for Disease Control and Prevention; Children's Hospital Medical Center, Cincinnati; Kaiser Permanente
• Investigators: Principal Investigator: Michael J Smith, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: COVID vaccine; Fever following vaccination
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Seizures; Hyperthermia; Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: Pro00113014

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