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

• ClinicalTrials.gov Identifier: NCT05540522
• Recruitment Status: Completed
• First Posted: September 14, 2022
• Last Update Posted: April 3, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 8, 2022
• First Posted Date: September 14, 2022
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: September 12, 2022
• Actual Primary Completion Date: March 12, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2023)

• The proportion of participants reporting laboratory-confirmed influenza (LCI) cases with associated per-protocol influenza-like illness (ILI) in each vaccine group, 18 through 64 years of age [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting laboratory-confirmed influenza (LCI) cases with associated per-protocol influenza-like illness (ILI) in each vaccine group, ≥65 years of age [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• Percentage of participants reporting local reactions, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: For up to 7 days following vaccination ]
  Pain at the injection site, redness, and swelling
• Percentage of participants reporting systemic events, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: For up to 7 days following vaccination ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain
• Percentage of participants reporting adverse events, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: From the time the participant provides informed consent through 4 weeks after vaccination ]
  As elicited by investigational site staff
• Percentage of participants reporting serious adverse events, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: From the time the participant provides informed consent through 6 months after vaccination ]
  As elicited by investigational site staff

Original Primary Outcome Measures (submitted: September 12, 2022)

• The proportion of participants reporting laboratory-confirmed influenza (LCI) cases with associated per-protocol influenza-like illness (ILI) in each vaccine group, 18 through 64 years of age and ≥65 years of age combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• Geometric mean ratio (GMR) of hemagglutination inhibition (HAI) titers for each strain in qIRV recipients compared to QIV recipients, 18 through 64 and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• Difference in percentage of participants achieving seroconversion for each strain between qIRV recipients and QIV recipients, 18 through 64 and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• Percentage of participants reporting local reactions, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: For up to 7 days following vaccination ]
  Pain at the injection site, redness, and swelling
• Percentage of participants reporting systemic events, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: For up to 7 days following vaccination ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain
• Percentage of participants reporting adverse events, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: From the time the participant provides informed consent through 4 weeks after vaccination ]
  As elicited by investigational site staff
• Percentage of participants reporting serious adverse events, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: From the time the participant provides informed consent through 6 months after vaccination ]
  As elicited by investigational site staff

Current Secondary Outcome Measures (submitted: July 14, 2023)

• The proportion of participants reporting LCI cases with associated per-protocol ILI caused by all matched strains, each matched strain, or unmatched strains in each vaccine group, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting culture-confirmed influenza (CCI) cases with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI associated with ILI, as defined by applying a modified CDC definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI cases associated with ILI, as defined by applying the WHO definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting cases of influenza, as confirmed by central RT-PCR, local RT-PCR or culture, with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• Geometric mean ratio (GMR) of hemagglutination inhibition (HAI) titers for each strain in qIRV recipients compared to QIV recipients, 18 through 64 and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• Difference in percentage of participants achieving seroconversion for each strain between qIRV recipients and QIV recipients, 18 through 64 and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• HAI geometric mean titers (GMTs) for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• HAI geometric mean fold rise (GMFR) for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• The proportion of participants achieving HAI seroconversion for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• The proportion of participants with HAI titers ≥1:40 for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: Baseline and 4 weeks after vaccination ]
  As measured at the central laboratory

Original Secondary Outcome Measures (submitted: September 12, 2022)

• GMR of HAI titers for each A strain in qIRV recipients compared to QIV recipients, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• Difference in percentage achieving seroconversion for each A strain between qIRV recipients and QIV recipients, 18 through 64 and ≥65 years of age separately [ Time Frame: 4 weeks after vaccination ]
  As measured at the central laboratory
• HAI geometric mean titers (GMTs) for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• HAI geometric mean fold rise (GMFR) for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: Before vaccination and at 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• The proportion of participants achieving HAI seroconversion for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• The proportion of participants with HAI titers ≥1:40 for each strain, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: Before vaccination and at 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• The proportion of participants achieving HAI seroconversion for all strains, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: At 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• The proportion of participants with HAI titers ≥1:40 for all strains, 18 through 64 years of age and ≥65 years of age separately [ Time Frame: Before vaccination and at 4 weeks and 6 months after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI cases with associated per-protocol ILI in each vaccine group, ≥65 years of age [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI cases with associated per-protocol ILI in each vaccine group, 18 through 64 years of age [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI cases with associated per-protocol ILI caused by all matched strains or each matched strain in each vaccine group, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting culture-confirmed influenza (CCI) cases with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI associated with ILI, as defined by applying a modified CDC definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting LCI cases associated with ILI, as defined by applying the WHO definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory
• The proportion of participants reporting cases of influenza, as confirmed by local RT-PCR or culture, with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately and combined [ Time Frame: At least 14 days after vaccination ]
  As measured at the central laboratory

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate a Modified RNA Vaccine Against Influenza in Adults 18 Years of Age or Older
• Official Title: A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA COMPARED TO LICENSED INACTIVATED INFLUENZA VACCINE IN HEALTHY ADULTS 18 YEARS OF AGE OR OLDER
• Brief Summary: 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.

Detailed Description

This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a quadrivalent influenza modRNA vaccine (qIRV) encoding HA of 4 seasonally recommended strains (2 A strains and 2 B strains) compared to licensed quadrivalent influenza vaccine (QIV) in healthy adults 18 years of age and older.

Participants may be enrolled in either the reactogenicity subset, immunogenicity subset, or both/neither subset(s). Efficacy will be assessed in this study through surveillance for influenza-like illness.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Prevention

• Condition: Influenza, Human

Intervention

• Biological: Quadrivalent influenza modRNA vaccine
  Quadrivalent influenza modRNA vaccine (single dose)
• Biological: Quadrivalent influenza vaccine
  Licensed quadrivalent influenza vaccine (single dose)

Study Arms

• Experimental: Quadrivalent influenza modRNA vaccine, 18 through 64 years of age
  Quadrivalent influenza modRNA vaccine (single dose), participants 18 through 64 years of age
  Intervention: Biological: Quadrivalent influenza modRNA vaccine
• Active Comparator: Quadrivalent influenza vaccine, 18 through 64 years of age
  Licensed quadrivalent influenza vaccine (single dose), participants 18 through 64 years of age
  Intervention: Biological: Quadrivalent influenza vaccine
• Experimental: Quadrivalent influenza modRNA vaccine, ≥65 years of age
  Quadrivalent influenza modRNA vaccine (single dose), participants ≥65 years of age
  Intervention: Biological: Quadrivalent influenza modRNA vaccine
• Active Comparator: Quadrivalent influenza vaccine, ≥65 years of age
  Licensed quadrivalent influenza vaccine (single dose), participants ≥65 years of age
  Intervention: Biological: Quadrivalent influenza vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2024): 46169
• Original Estimated Enrollment (submitted: September 12, 2022): 25000
• Actual Study Completion Date: March 12, 2024
• Actual Primary Completion Date: March 12, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female participants ≥18 years of age at Visit 1 (Day 1).
2. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
4. Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. Medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality, that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
2. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
3. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
4. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
5. Allergy to egg proteins (egg or egg products) or chicken proteins.
6. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
7. Receipt of blood/plasma products or immunoglobulin from 60 days before study intervention administration, or planned receipt throughout the study.
8. Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza.
9. Any participant who has received or plans to receive a modRNA-platform SARS CoV-2 vaccine within 14 days before or after study vaccination at Visit 1.
10. Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in this study.
11. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Chile, New Zealand, Philippines, South Africa, United States

Administrative Information

• NCT Number: NCT05540522
• Other Study ID Numbers: C4781004
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024