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A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Modified RNA Vaccine Against Influenza

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05052697
Recruitment Status : Recruiting
First Posted : September 22, 2021
Last Update Posted : July 21, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

This study will be divided into two substudies - Substudy A (SSA) and Substudy B (SSB)

Substudy A This is a Phase 1 randomized substudy to evaluate the safety and immunogenicity of monovalent influenza modRNA vaccine (mIRV) and bivalent influenza modRNA vaccine (bIRV) at various dose levels, and quadrivalent influenza modRNA vaccine (qIRV), in participants 65 to 85 years of age. Participants will receive at Vaccination 1 either:

  • 1 of 4 dose levels of mIRV (either A or B Strain),
  • 1 of 4 dose levels of bIRV (containing both A and B strains),
  • qIRV (at 1 dose level), or
  • A licensed quadrivalent influenza vaccine (QIV).

At approximately 8 weeks following Vaccination 1, participants will be unblinded and QIV (Vaccination 2) administered to participants not having previously received this at Vaccination 1. Additionally, participants who previously received QIV at Vaccination 1 will receive one of the following for Vaccination 2:

  • mIRV encoding A strain at dose level 4, or
  • mIRV encoding B strain at dose level 4.

Substudy B

This is a randomized substudy to evaluate the safety and immunogenicity of the following vaccination schedules in participants 65 to 85 years of age:

2-Visit Schedules

  • 2 doses of qIRV (at a dose level 1), administered 21 days apart.
  • 2 doses of licensed QIV, administered 21 days apart (as a control group)
  • A dose of licensed QIV following by a dose of bIRV encoding 2 A strains at dose level combination 1 or 2, administered 21 days apart.

    1-Visit Schedules

  • A dose of licensed QIV administered concurrently in the opposite arm with bIRV encoding 2 A strains at dose level combination 1 or 2.
  • A dose of bIRV encoding 2 A strains administered concurrently in the opposite arm with a dose of bIRV encoding 2 B strains.at dose level 1.
  • A dose of qIRV encoding 2 A strains and 2 B strains at dose level 2 (at one of two possible dose level combinations).
  • A dose of qIRV encoding 2 A strains and 2 B strains at dose level 3.
  • 1 dose of licensed QIV (as a control group).

Condition or disease Intervention/treatment Phase
Influenza, Human Biological: mIRV Biological: bIRV AB Biological: qIRV Biological: QIV Biological: bIRV AA Biological: bIRV BB Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 615 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: SSA: observer-blinded, sponsor unblind SSB: single-blind, sponsor unblind
Primary Purpose: Prevention
Official Title: A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA IN HEALTHY INDIVIDUALS
Actual Study Start Date : September 13, 2021
Estimated Primary Completion Date : January 9, 2023
Estimated Study Completion Date : January 9, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot Vaccines

Arm Intervention/treatment
Experimental: SSA: mIRV A (dose level 1) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV A (dose level 2) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV A (dose level 3) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV A (dose level 4) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV B (dose level 1) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV B (dose level 2) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV B (dose level 3) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: mIRV B (dose level 4) + QIV Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: bIRV AB (dose level combination 1) + QIV Biological: bIRV AB
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: bIRV AB (dose level combination 2) + QIV Biological: bIRV AB
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: bIRV AB (dose level combination 3) + QIV Biological: bIRV AB
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: bIRV AB (dose level combination 4) + QIV Biological: bIRV AB
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: QIV + mIRV A strain (dose level 4) Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: qIRV (dose level 1) + QIV Biological: qIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSA: QIV + mIRV B strain (dose level 4) Biological: mIRV
Intramuscular injection

Biological: QIV
Intramuscular injection

Experimental: SSB: 2 doses of qIRV (dose level 1), 2-visit schedule Biological: qIRV
Intramuscular injection

Experimental: SSB: 2 doses of QIV, 2-visit schedule Biological: QIV
Intramuscular injection

Experimental: SSB: QIV + bIRV AA (dose level combination 1), 2-visit schedule Biological: QIV
Intramuscular injection

Biological: bIRV AA
Intramuscular injection

Experimental: SSB: QIV + bIRV AA (dose level combination 2), 2-visit schedule Biological: QIV
Intramuscular injection

Biological: bIRV AA
Intramuscular injection

Experimental: SSB: QIV + bIRV AA (dose level combination 1), 1-visit schedule Biological: QIV
Intramuscular injection

Biological: bIRV AA
Intramuscular injection

Experimental: SSB: QIV + bIRV AA (dose level combination 2), 1-visit schedule Biological: QIV
Intramuscular injection

Biological: bIRV AA
Intramuscular injection

Experimental: SSB: qIRV (dose level 2, dose combination 1), 1-visit schedule
NOTE: Arm Description has not been entered.
Biological: qIRV
Intramuscular injection

Experimental: SSB: qIRV (dose level 2, dose combination 2), 1-visit schedule
NOTE: Arm Description has not been entered
Biological: qIRV
Intramuscular injection

Experimental: SSB: qIRV (dose level 3), 1-visit schedule
NOTE: Arm Description has not been entered
Biological: qIRV
Intramuscular injection

Experimental: SSB: bIRV AA + bIRV BB (both dose level combination 1), 1-visit schedule
NOTE: Arm Description has not been entered
Biological: bIRV AA
Intramuscular injection

Biological: bIRV BB
Intramuscular injection

Experimental: SSB: 1 dose of QIV, 1-visit schedule
NOTE: Arm Description has not been entered
Biological: QIV
Intramuscular injection




Primary Outcome Measures :
  1. SSA: Percentage of participants reporting local reactions [ Time Frame: For 7 days after Vaccinations 1 and 2 ]
    Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.

  2. SSA: Percentage of participants reporting systemic events [ Time Frame: For 7 days after Vaccinations 1 and 2 ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self reported in electronic diaries.

  3. SSA: Percentage of participants reporting adverse events [ Time Frame: From vaccination to 4 weeks after Vaccinations 1 and 2 ]
    As elicited by investigational site staff.

  4. SSA: Percentage of participants reporting serious adverse events [ Time Frame: From vaccination to 6 months after the last study vaccination ]
    As elicited by investigational site staff.

  5. SSA: Percentage of participants with abnormal hematology and chemistry laboratory values [ Time Frame: 2 days after Vaccination 1 ]
    As measured at the central laboratory

  6. SSA: Percentage of participants with abnormal hematology and chemistry laboratory values [ Time Frame: 1 week after Vaccination 1 ]
    As measured at the central laboratory

  7. SSA: Percentage of participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 2 days after Vaccination 1 ]
    As measured at the central laboratory

  8. SSA: Percentage of participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 1 week after Vaccination 1 ]
    As measured at the central laboratory

  9. SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities [ Time Frame: 2 days after Vaccination 1 ]
    ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist

  10. SSA: Percentage of participants with new ECG abnormalities [ Time Frame: 1 week after Vaccination 1 ]
    ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist

  11. SSB: Percentage of participants reporting local reactions [ Time Frame: For 7 days after each vaccination ]
    Pain at the injection site, redness, and swelling, as self-reported in electronic diaries.

  12. SSB: Percentage of participants reporting systemic events [ Time Frame: For 7 days after each vaccination ]
    Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self reported in electronic diaries.

  13. SSB: Percentage of participants reporting adverse events [ Time Frame: From Vaccination 1 to 4 weeks after the last vaccination ]
    As elicited by investigational site staff.

  14. SSB: Percentage of participants reporting serious adverse events [ Time Frame: From Vaccination 1 to 6 months after the last vaccination ]
    As elicited by investigational site staff.

  15. SSB: Percentage of participants with abnormal troponin I laboratory values [ Time Frame: 2 days after the last vaccination ]
    As measured at the central laboratory

  16. SSB: Percentage of participants with new ECG abnormalities [ Time Frame: 2 days after the last vaccination ]
    ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist


Secondary Outcome Measures :
  1. SSA: Geometric mean titers (GMTs) of hemagglutination inhibition (HAI) titers [ Time Frame: At Baseline, and 1-, 4- and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory

  2. SSA: Geometric mean fold rise (GMFR) in HAI titers from before vaccination to each subsequent timepoint [ Time Frame: At 1-, 4-, and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory

  3. SSA: Proportion of participants achieving HAI seroconversion for each strain [ Time Frame: At 1-, 4-, and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory

  4. SSA: Proportion of participants with HAI titer >=1:40 for each strain [ Time Frame: At Baseline, and 1-, 4-, and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory.

  5. SSA: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants achieving HAI seroconversion for all strains [ Time Frame: At 1-, 4-, and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory

  6. SSA: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants with HAI titer >=1:40 for all strains [ Time Frame: At Baseline, and 1-, 4-, and 8-weeks after Vaccination 1 ]
    As measured at the central laboratory.

  7. SSA: The geometric mean ratio (GMR) of the geometric mean of HAI titers from participants receiving qIRV to the geometric mean of HAI titers from participants receiving QIV [ Time Frame: At 4 weeks after Vaccination 1 ]
    As measured at the central laboratory

  8. SSA: The difference in percentage of participants achieving HAI seroconversion for each strain in qIRV recipients compared to licensed QIV recipients [ Time Frame: At 4 week after Vaccination 1 ]
    As measured at the central laboratory

  9. SSB: GMTs of HAI titers [ Time Frame: At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4- and 8-weeks after the last vaccination ]
    As measured at the central laboratory

  10. SSB: GMFR in HAI titers from before vaccination to each subsequent timepoint [ Time Frame: Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination ]
    As measured at the central laboratory

  11. SSB: Proportion of participants achieving HAI seroconversion for each strain [ Time Frame: Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination ]
    As measured at the central laboratory

  12. SSB: Proportion of participants with HAI titer >=1:40 for each strain [ Time Frame: At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4-, and 8-weeks after the last vaccination ]
    As measured at the central laboratory.

  13. SSB: In participants who receive either qIRV or QIV, the proportion of participants achieving HAI seroconversion for all strains [ Time Frame: Prior to Vaccination 2 (if applicable), and at 1-, 4-, and 8-weeks after the last vaccination ]
    As measured at the central laboratory

  14. SSA: In participants who receive either qIRV or QIV at Vaccination 1, the proportion of participants with HAI titer >=1:40 for all strains [ Time Frame: At Baseline, prior to Vaccination 2 (if applicable), and 1-, 4-, and 8-weeks after the last vaccination ]
    As measured at the central laboratory.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Substudy A

Inclusion Criteria:

  • Male or female participants 65 to 85 years of age.
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • 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.
  • Male participant who is able to father children and willing to use an acceptable method of contraception; or female participant not of childbearing potential; or male participant not able to father children.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • Other 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Allergy to egg proteins (egg or egg products) or chicken proteins.
  • Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 1
  • Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 1 that has not been confirmed as negative.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
  • Vaccination with any influenza vaccine within 6 months (175 days) before study intervention administration.
  • Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 60 days of Visit 1
  • Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
  • Screening hematology/blood chemistry lab >=Grade 1 abnormality. Except Bilirubin, other stable Grade1 abnormalities may be considered eligible by Investigator.
  • Screening ECG that is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or study results.
  • Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Participation in strenuous or endurance exercise through Visit 3.
  • Prior history of heart disease.

Substudy B

Inclusion Criteria:

  • Male or female participants 65 to 85 years of age.
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • 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.
  • Male participant who is able to father children and willing to use an acceptable method of contraception; or female participant not of childbearing potential; or male participant not able to father children.
  • Participants who have received licensed influenza vaccination for the 2021-2022 northern hemisphere season >4 months (120 days) before study intervention administration.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • Other 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.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
  • Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  • Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Women who are pregnant or breastfeeding.
  • Allergy to egg proteins (egg or egg products) or chicken proteins.
  • Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 201
  • Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 201 that has not been confirmed as negative.
  • Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  • Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
  • Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 28 days of Visit 201
  • Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
  • Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
  • Participation in strenuous or endurance exercise through Visit 205.
  • Prior history of heart disease.
  • Any abnormal screening troponin I laboratory value
  • Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05052697


Contacts
Layout table for location contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Show Show 93 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05052697    
Other Study ID Numbers: C4781001
First Posted: September 22, 2021    Key Record Dates
Last Update Posted: July 21, 2022
Last Verified: July 2022
Individual Participant Data (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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Grippe
Flu
Influenza
Vaccine
RNA vaccine
Additional relevant MeSH terms:
Layout table for MeSH terms
Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases