A Study About Modified RNA Vaccines Against Influenza in Healthy Adults

A STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF MODIFIED RNA VACCINES AGAINST INFLUENZA IN HEALTHY ADULTS

The purpose of this study is to learn if modified RNA (modRNA) vaccines for the prevention of influenza are:

• safe; and
• how these vaccines produce an immune response in generally healthy adults. Immune response is the way the body protects itself against things it sees as harmful or foreign.

RNA (also called ribonucleic acid) is one of two types of nucleic acid made by cells. RNA contains information that has been copied from DNA (the other type of nucleic acid). Cells make several different forms of RNA, and each form has a specific job in the cell. Many forms of RNA have functions related to making proteins. RNA is also the genetic material of some viruses instead of DNA. RNA can be made in the laboratory and used in research studies. Also called ribonucleic acid.

Influenza is term used for flu illness. It is an infection caused by a virus that affects your mouth, nose, and throat.

The study is seeking for participants who:

• are at least 18 years of age
• have not received an influenza vaccine within the last 6 months
• are generally healthy

This study will be divided into three sub-studies: Substudy A (SSA), Substudy B (SSB), and Substudy C (SSC).

All participants, regardless of sub-study, will receive 1 dose of either of the following vaccines as an injection into their arm:

• 1 of the modRNA influenza vaccines that is being studied; or
• an approved influenza vaccine approved for use in their respective age group.

Participants will be involved in this study for about 6 months. During this time, participants will have at least 3 clinic visits.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: Influenza ModRNA Vaccine; Biological: Quadrivalent Influenza Vaccine (QIV)

• Study Type: Interventional
• Enrollment (Actual): 1202
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • AMR Clinical
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Headlands Research - Scottsdale
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Lake Forest, California, United States, 92630
      • Orange County Research Center
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )
    • Miami Lakes, Florida, United States, 33014
      • Palm Springs Community Health Center
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32819
      • Headlands Research Orlando
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Alliance for Multispecialty Research, LLC
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research LLC dba Nucleus Network
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research, LLC
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Durham, North Carolina, United States, 27703
      • Duke Vaccine and Trials Unit
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • DM Clinical Research - Philadelphia
  • Texas
    • Brownsville, Texas, United States, 78526
      • Headlands Horizons LLC
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC dba Flourish Research
    • Tomball, Texas, United States, 77375
      • Dynamed Clinical Research, LP d/b/a DM Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Norfolk, Virginia, United States, 23502
      • AMR Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria

Applies to all 3 substudies:

• participants ≥18 years of age.
• generally healthy participants.

Substudy C ONLY:

- receipt of licensed influenza vaccination for the 2023-2024 flu season at least 6 months ago.

Key Exclusion Criteria

All 3 substudies:

• diagnosis of influenza (by clinical testing) in the last 6 months.
• immunocompromised individuals with known or suspected immunodeficiency
• receipt of any investigational or licensed influenza vaccines within 6 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

19

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSA: Influenza ModRNA Vaccine 2A; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSA: Influenza ModRNA Vaccine 3A; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSA: Influenza ModRNA Vaccine 4A; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSA: Influenza ModRNA Vaccine 5A; - Single dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Active Comparator: SSA: QIV1; - Single dose on Day 1	Biological: Quadrivalent Influenza Vaccine (QIV); Intramuscular injection
Experimental: SSB: Influenza ModRNA Vaccine 3B; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSB: Influenza ModRNA Vaccine 4B; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSB: Influenza ModRNA Vaccine 5B; - Single dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Active Comparator: SSB: QIV2; - Single Dose on Day 1	Biological: Quadrivalent Influenza Vaccine (QIV); Intramuscular injection
Active Comparator: SSB: QIV3; - Single Dose on Day 1	Biological: Quadrivalent Influenza Vaccine (QIV); Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 3C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 4C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 5C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 6C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 7C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 8C; - Single Dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Experimental: SSC: Influenza ModRNA Vaccine 9C; - Single dose on Day 1	Biological: Influenza ModRNA Vaccine; Intramuscular injection
Active Comparator: SSC: QIV2; - Single Dose on Day 1	Biological: Quadrivalent Influenza Vaccine (QIV); Intramuscular injection
Active Comparator: SSC: QIV3; - Single Dose on Day 1	Biological: Quadrivalent Influenza Vaccine (QIV); Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the electronic dairy (e-diary) or by investigators in case report form (CRF) after vaccination. All local reactions were graded based on center for biologics evaluation and research (CBER) toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSB: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the e-diary or by investigators in CRF after vaccination. All local reactions were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSC: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in the e-diary or by investigators in CRF after vaccination. All local reactions were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any local reaction of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSA: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination	Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSB: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination	Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSC: Percentage of Participants With Systemic Events for up to 7 Days Following Vaccination	Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and joint pain) were recorded by participants in the e-diary or by investigators in CRF after vaccination. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure, data is reported as percentage of participants with any systemic events of any grade.	From Day 1 through Day 7 after study vaccination [Vaccination on Day 1]
SSA: Percentage of Participants With Adverse Events (AEs) From Vaccination Through 4 Weeks After Vaccination	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.	From study vaccination on Day 1 through 4 weeks after study vaccination
SSB: Percentage of Participants With AEs From Vaccination Through 4 Weeks After Vaccination	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.	From study vaccination on Day 1 through 4 weeks after study vaccination
SSC: Percentage of Participants With AEs From Vaccination Through 4 Weeks After Vaccination	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.	From study vaccination on Day 1 through 4 weeks after study vaccination
SSA: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator.	From study vaccination on Day 1 through 6 months after study vaccination
SSB: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator.	From study vaccination on Day 1 through 6 months after study vaccination
SSC: Percentage of Participants With SAEs From Vaccination Through 6 Months After Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, any other pre-specified criteria in protocol of the study or other important medical event judged by the investigator.	From study vaccination on Day 1 through 6 months after study vaccination
SSA: Percentage of Participants With Medically Attended Adverse Events (MAEs) From Vaccination Through 6 Months After Vaccination	An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility.	From study vaccination on Day 1 through 6 months after study vaccination
SSB: Percentage of Participants With MAEs From Vaccination Through 6 Months After Vaccination	An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility.	From study vaccination on Day 1 through 6 months after study vaccination
SSC: Percentage of Participants With MAEs From Vaccination Through 6 Months After Vaccination	An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility.	From study vaccination on Day 1 through 6 months after study vaccination
SSA: Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Vaccination Through 6 Months After Vaccination	An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma).	From study vaccination on Day 1 through 6 months after study vaccination
SSB: Percentage of Participants With NDCMCs From Vaccination Through 6 Months After Vaccination	An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma).	From study vaccination on Day 1 through 6 months after study vaccination
SSC: Percentage of Participants With NDCMCs From Vaccination Through 6 Months After Vaccination	An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects (e.g., asthma).	From study vaccination on Day 1 through 6 months after study vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition Assay (HAI) Titers at Baseline and 4 Weeks After Vaccination	GMTs and the corresponding 2-sided 95% confidence intervals (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution).	Baseline (before study vaccination on Day 1), 4 weeks after study vaccination
SSA: Geometric Mean Fold Rise (GMFR) of Strain-Specific HAI Titers From Before Vaccination to 4 Weeks After Vaccination	GMFR was defined as the geometric mean of the fold rise in the assay results from before vaccination to a specified time point after vaccination.	From before study vaccination on Day 1 up to 4 weeks after study vaccination
SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination	Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with at least a 4-fold rise at the time point of interest.	4 weeks after study vaccination
SSA: Percentage of Participants With HAI Titers >=1:40 For Each Strain at Baseline and 4 Weeks After Vaccination	This measure is for percentage of participants achieving HAI titers >=1:40 for each strain.	Baseline (before study vaccination on Day 1), 4 weeks after study vaccination
SSB: GMTs of Strain-Specific HAI Titers at Baseline and 4 Weeks After Vaccination		Baseline (before study vaccination on Day 1), 4 weeks after study vaccination
SSB: GMFRs of Strain-Specific HAI Titers From Before Vaccination to 4 Weeks After Vaccination		From before study vaccination on Day 1 up to 4 weeks after study vaccination
SSB: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination		4 weeks after study vaccination
SSB: Percentage of Participants With HAI Titers >=1:40 For Each Strain at Baseline and 4 Weeks After Vaccination	This measure is for percentage of participants achieving HAI titers >=1:40 for each strain.	Baseline (before study vaccination on Day 1), 4 weeks after study vaccination

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2024
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): May 31, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines
• Other Study ID Numbers: C4781013; NCT06436703 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No