NCT05540522

A Study to Evaluate a Modified RNA Vaccine Against Influenza in Adults 18 Years of Age or Older

Completed Phase 3 Results posted Last updated 8 May 2025

What this trial tests

Phase 3 trial testing Quadrivalent influenza modRNA vaccine in Influenza, Human in 45,789 participants. Completed in 12 March 2024.

Timeline

12 September 2022

Primary endpoint
12 March 2024

12 March 2024

Quick facts

Lead sponsor	Pfizer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	45,789
Start date	12 September 2022
Primary completion	12 March 2024
Estimated completion	12 March 2024
Sites	321 locations across New Zealand, South Africa, Chile, Philippines, Argentina, United States

Drugs / interventions tested

• Quadrivalent influenza modRNA vaccine (quadrivalent-influenza-modrna-vaccine) — full drug profile →
• Quadrivalent influenza vaccine — full drug profile →

Conditions studied

• Influenza, Human — all drugs for Influenza, Human →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Influenza, Human. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Reporting First Episode of LCI Cases With Associated Per-Protocol ILI Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years Primary · Day 15 to surveillance cut-off (approximately 6 months)

LCI was defined as influenza infection confirmed through through reverse transcription- polymerase chain reaction (RT-PCR) or culture at the central laboratory, unless otherwise specified. Per-protocol ILI was defined as occurrence (new onset or worsening of preexisting condition) of at least 1 respiratory symptoms concurrently with at least 1 systemic symptoms. Data was obtained during the 2022-2023 northern hemisphere influenza season up to surveillance cut-off decided by Sponsor.

Group	Value	95% CI
qIRV: 18-64 Years	0.63
Licensed QIV: 18-64 Years	0.95

Percentage of Participants Reporting First Episode of Laboratory-Confirmed Influenza (LCI) Cases With Associated Per-Protocol Influenza-Like Illness (ILI) Caused by Any Strain at Least 14 Days After Vaccination: >= 65 Years Primary · Day 15 up to primary surveillance cut-off (approximately 1 year)

LCI was defined as influenza infection confirmed through RT-PCR or culture at the central laboratory, unless otherwise specified. Per-protocol ILI was defined as occurrence (new onset or worsening of preexisting condition) of at least 1 respiratory symptoms concurrently with at least 1 systemic symptoms. Data was obtained during the 2022-2023 northern and southern hemisphere influenza season up to surveillance cut-off decided by Sponsor.

Group	Value	95% CI
qIRV: >=65 Years	0.59
Licensed QIV: >=65 Years	0.56

Percentage of Participants Reporting Any Local Reactions Within 7 Days After Study Vaccination: 18-64 Years Primary · From Day 1 to Day 7 after study vaccination

Local reactions included redness, swelling and pain at the injection site and were recorded by participants in an e-diary. 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 for any local reaction and any grade.

Group	Value	95% CI
qIRV: 18-64 Years	70.1	68.5 – 71.7
Licensed QIV: 18-64 Years	43.1	41.3 – 44.9

Percentage of Participants Reporting Any Local Reactions Within 7 Days After Study Vaccination: >=65 Years Primary · From Day 1 to Day 7 after study vaccination

Local reactions included redness, swelling and pain at the injection site and were recorded by participants in an e-diary. 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 for any local reaction and any grade.

Group	Value	95% CI
qIRV: >=65 Years	68.7	67.2 – 70.3
Licensed QIV: >=65 Years	25.8	24.4 – 27.3

Percentage of Participants Reporting Any Systemic Events Within 7 Days After Study Vaccination: 18-64 Years Primary · From Day 1 to Day 7 after study vaccination

Systemic events (vomiting, diarrhoea, headache, Fatigue/tiredness, chills, new or worsened muscle pain and joint pain) were recorded by participants in an e-diary. 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 for any systemic reaction and any grade.

Group	Value	95% CI
qIRV: 18-64 Years	65.8	64.0 – 67.4
Licensed QIV: 18-64 Years	48.7	46.9 – 50.5

Percentage of Participants Reporting Any Systemic Events Within 7 Days After Study Vaccination: >=65 Years Primary · From Day 1 to Day 7 after study vaccination

Systemic events (vomiting, diarrhoea, headache, Fatigue/tiredness, chills, new or worsened muscle pain and joint pain) were recorded by participants in an e-diary. 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 for any systemic reaction and any grade.

Group	Value	95% CI
qIRV: >=65 Years	58.6	57.0 – 60.2
Licensed QIV: >=65 Years	34.9	33.3 – 36.4

Percentage of Participants Reporting Adverse Events (AEs) From Study Vaccination Through 4 Weeks After Study Vaccination: 18-64 Years Primary · From study vaccination on Day 1 through 4 weeks after study vaccination

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.

Group	Value	95% CI
qIRV: 18-64 Years	6.7	6.2 – 7.3
Licensed QIV: 18-64 Years	4.9	4.5 – 5.4

Percentage of Participants Reporting AEs From Study Vaccination Through 4 Weeks After Study Vaccination: >=65 Years Primary · From study vaccination on Day 1 through 4 weeks after study vaccination

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.

Group	Value	95% CI
qIRV: >=65 Years	8.7	8.2 – 9.1
Licensed QIV: >=65 Years	5.9	5.5 – 6.3

Percentage of Participants Reporting AEs From Study Vaccination Through 4 Weeks After Study Vaccination: >=18 Years Primary · From study vaccination on Day 1 through 4 weeks after study vaccination

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.

Group	Value	95% CI
qIRV (>=18 Years)	7.9	7.5 – 8.2
Licensed QIV (>=18 Years)	5.5	5.2 – 5.8

Percentage of Participants Reporting Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination: 18-64 Years Primary · From Day 1 up to 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.

Group	Value	95% CI
qIRV: 18-64 Years	0.9	0.7 – 1.1
Licensed QIV: 18-64 Years	1.0	0.8 – 1.2

Percentage of Participants Reporting SAEs From Study Vaccination Through 6 Months After Study Vaccination: >=65 Years Primary · From Day 1 up to 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.

Group	Value	95% CI
qIRV: >=65 Years	2.3	2.1 – 2.6
Licensed QIV: >=65 Years	2.2	1.9 – 2.4

Percentage of Participants Reporting SAEs From Study Vaccination Through 6 Months After Study Vaccination: >=18 Years Primary · From Day 1 up to 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.

Group	Value	95% CI
qIRV (>=18 Years)	1.8	1.6 – 1.9
Licensed QIV (>=18 Years)	1.7	1.5 – 1.9

Adverse events — posted to ClinicalTrials.gov

Time frame: Local reactions/systemic events (Systematic assessment): from Day 1 to Day 7 after vaccination; Non-systematic assessment: SAEs: from vaccination 1 up to 6 months after last vaccination, other AEs: from vaccination 1 up to 4 weeks after last vaccination and All-cause mortality: From vaccination on Day 1 up to 6 months after vaccination.. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

qIRV: 18-64 Years

Serious: 83/9191 (1%)

Deaths: 7/9191

Licensed QIV: 18-64 Years

Serious: 93/9197 (1%)

Deaths: 9/9197

qIRV: >=65 Years

Serious: 318/13557 (2%)

Deaths: 49/13557

Licensed QIV: >=65 Years

Serious: 296/13611 (2%)

Deaths: 46/13611

qIRV (>=18 Years)

Serious: 401/22787 (2%)

Deaths: 56/22787

Licensed QIV: >=18 Years

Serious: 389/22808 (2%)

Deaths: 55/22808

Serious adverse events (487 terms)

Reaction	System	qIRV: 18-64 Years	Licensed QIV: 18-64 Years	qIRV: >=65 Years	Licensed QIV: >=65 Years	qIRV (>=18 Years)	Licensed QIV: >=18 Years
Pneumonia	Infections and infestations	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—	—
Death	General disorders	—	—	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Cardio-respiratory arrest	Cardiac disorders	—	—	—	—	—	—
Appendicitis	Infections and infestations	—	—	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	qIRV: 18-64 Years	Licensed QIV: 18-64 Years	qIRV: >=65 Years	Licensed QIV: >=65 Years	qIRV (>=18 Years)	Licensed QIV: >=18 Years
Injection site pain (PAIN)	General disorders	—	—	—	—	—	—
Fatigue (FATIGUE)	General disorders	—	—	—	—	—	—
Headache (HEADACHE)	Nervous system disorders	—	—	—	—	—	—
Myalgia (MUSCLE PAIN)	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Chills (CHILLS)	General disorders	—	—	—	—	—	—
Arthralgia (JOINT PAIN)	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Injection site swelling (SWELLING)	General disorders	—	—	—	—	—	—
Diarrhoea (DIARRHEA)	Gastrointestinal disorders	—	—	—	—	—	—
Injection site erythema (REDNESS)	General disorders	—	—	—	—	—	—
Injection site pain	General disorders	—	—	—	—	—	—
Pyrexia (FEVER)	General disorders	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Atrial fibrillation, Acute respiratory failure, Acute kidney injury, Cardiac failure congestive, Chronic obstructive pulmonary disease, Acute myocardial infarction, Sepsis.

Data from ClinicalTrials.gov NCT05540522 adverse events section.

Sponsor's own description

This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a single dose of a quadrivalent influenza modRNA vaccine compared to licensed inactivated influenza vaccine in healthy adults 18 years of age and older.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. mRNA vaccines for infectious diseases - advances, challenges and opportunities.
   Pardi N, Krammer F. · · 2024 · cited 111× · PMID 39367276 · DOI 10.1038/s41573-024-01042-y
2. A comprehensive comparison of DNA and RNA vaccines.
   Wang C, Yuan F. · · 2024 · cited 42× · PMID 38810703 · DOI 10.1016/j.addr.2024.115340
3. mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV.
   Matarazzo L, Bettencourt PJG. · · 2023 · cited 35× · PMID 37168860 · DOI 10.3389/fimmu.2023.1172691
4. Seasonal influenza vaccine performance and the potential benefits of mRNA vaccines.
   Russell CA, Fouchier RAM, Ghaswalla P, Park Y, et al · · 2024 · cited 28× · PMID 38619079 · DOI 10.1080/21645515.2024.2336357
5. From Co-Administration to Co-Formulation: The Race for New Vaccines against COVID-19 and Other Respiratory Viruses.
   Focosi D. · · 2023 · cited 16× · PMID 36679954 · DOI 10.3390/vaccines11010109
6. mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases.
   Brandi R, Paganelli A, D'Amelio R, Giuliani P, et al · · 2024 · cited 10× · PMID 39772079 · DOI 10.3390/vaccines12121418
7. Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines.
   Hauguel T, Sharma A, Mastrocola E, Lowry S, et al · · 2024 · cited 9× · PMID 39375384 · DOI 10.1038/s41541-024-00980-3
8. Race with virus evolution: The development and application of mRNA vaccines against SARS-CoV-2.
   Lee KM, Lin SJ, Wu CJ, Kuo RL. · · 2023 · cited 9× · PMID 36642222 · DOI 10.1016/j.bj.2023.01.002