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

NCT ID: NCT05052697

Last Updated: 2024-03-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

1158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-13

Study Completion Date

2023-01-27

Brief Summary

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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).

Substudy B

In participants 18 to 64 years of age:

-A dose of qIRV encoding 2 A strains and 2 B strains at a dose level combination 1 or 2.

Detailed Description

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Conditions

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Influenza, Human

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
SSA: observer-blinded, sponsor unblind SSB: single-blind, sponsor unblind

Study Groups

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SSA: mIRV A (dose level 1) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV A (dose level 2) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV A (dose level 3) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV A (dose level 4) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV B (dose level 1) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV B (dose level 2) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV B (dose level 3) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: mIRV B (dose level 4) + QIV

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: bIRV AB (dose level combination 1) + QIV

Group Type EXPERIMENTAL

bIRV AB

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: bIRV AB (dose level combination 2) + QIV

Group Type EXPERIMENTAL

bIRV AB

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: bIRV AB (dose level combination 3) + QIV

Group Type EXPERIMENTAL

bIRV AB

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: bIRV AB (dose level combination 4) + QIV

Group Type EXPERIMENTAL

bIRV AB

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: QIV + mIRV A strain (dose level 4)

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: qIRV (dose level 1) + QIV

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSA: QIV + mIRV B strain (dose level 4)

Group Type EXPERIMENTAL

mIRV

Intervention Type BIOLOGICAL

Intramuscular injection

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: 2 doses of qIRV (dose level 1), 2-visit schedule

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: 2 doses of QIV, 2-visit schedule

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

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

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

bIRV AA

Intervention Type BIOLOGICAL

Intramuscular injection

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

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

bIRV AA

Intervention Type BIOLOGICAL

Intramuscular injection

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

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

bIRV AA

Intervention Type BIOLOGICAL

Intramuscular injection

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

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

bIRV AA

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: qIRV (dose level 2, dose combination 1), 1-visit schedule

NOTE: Arm Description has not been entered.

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: qIRV (dose level 2, dose combination 2), 1-visit schedule

NOTE: Arm Description has not been entered

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: qIRV (dose level 3), 1-visit schedule

NOTE: Arm Description has not been entered

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: bIRV AA + bIRV BB (both dose level combination 1), 1-visit schedule

NOTE: Arm Description has not been entered

Group Type EXPERIMENTAL

bIRV AA

Intervention Type BIOLOGICAL

Intramuscular injection

bIRV BB

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: 1 dose of QIV, 1-visit schedule

NOTE: Arm Description has not been entered

Group Type EXPERIMENTAL

QIV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: qIRV (dose level 1), 1-visit schedule

NOTE: Arm Description has not been entered.

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

SSB: qIRV (dose level 2), 1-visit schedule

NOTE: Arm Description has not been entered.

Group Type EXPERIMENTAL

qIRV

Intervention Type BIOLOGICAL

Intramuscular injection

Interventions

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mIRV

Intramuscular injection

Intervention Type BIOLOGICAL

bIRV AB

Intramuscular injection

Intervention Type BIOLOGICAL

qIRV

Intramuscular injection

Intervention Type BIOLOGICAL

QIV

Intramuscular injection

Intervention Type BIOLOGICAL

bIRV AA

Intramuscular injection

Intervention Type BIOLOGICAL

bIRV BB

Intramuscular injection

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.


* Male or female participants 65 to 85 years of age or .Male or female participants 18 to 64 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.
* For participants 65 to 85 years of age at the time of enrollment, receipt of 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 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


* 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
* Any participant who has received licensed influenza vaccination for the 2022-2023 northern hemisphere influenza season.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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North Alabama Research Center

Athens, Alabama, United States

Site Status

The Heart Center

Athens, Alabama, United States

Site Status

Arizona Heart Rhythm Center

Phoenix, Arizona, United States

Site Status

HOPE Research Institute

Phoenix, Arizona, United States

Site Status

The Pain Center of Arizona

Phoenix, Arizona, United States

Site Status

Noble Clinical Research

Tucson, Arizona, United States

Site Status

Pima Heart and Vascular

Tucson, Arizona, United States

Site Status

Inland Valley Cardiovascular Center

Murrieta, California, United States

Site Status

Orange County Heart Institute

Orange, California, United States

Site Status

Artemis Institute for Clinical Research

Riverside, California, United States

Site Status

Orange County Research Center

Tustin, California, United States

Site Status

Pediatrics-Infectious Diseases - Clinical Trials Center at University of Colorado Anschutz Medical C

Aurora, Colorado, United States

Site Status

UCHealth Heart and Vascular Center - Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Yale Cardiology

New Haven, Connecticut, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, United States

Site Status

Halifax Health Medical Center

Daytona Beach, Florida, United States

Site Status

NYU Langone Cardiology Associates

Delray Beach, Florida, United States

Site Status

First Coast Heart & Vascular Center

Fleming Island, Florida, United States

Site Status

Fleming Island Center for Clinical Research

Fleming Island, Florida, United States

Site Status

Proactive Clinical Research,LLC

Fort Lauderdale, Florida, United States

Site Status

Alliance for Multispecialty Research, LLC

Fort Myers, Florida, United States

Site Status

Millennium Physician Group

Fort Myers, Florida, United States

Site Status

Robert B. Pritt, DO

Fort Myers, Florida, United States

Site Status

Direct Helpers Research Center.

Hialeah, Florida, United States

Site Status

Best Quality Research,Inc.

Hialeah, Florida, United States

Site Status

Elixia Infectious Disease, LLC

Hollywood, Florida, United States

Site Status

First Coast Heart & Vascular Center

Jacksonville, Florida, United States

Site Status

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare

Jacksonville, Florida, United States

Site Status

First Coast Cardiovascular Institute

Jacksonville, Florida, United States

Site Status

Premier Cardiology and Vascular Associates

Maitland, Florida, United States

Site Status

LMG Research

Miami, Florida, United States

Site Status

Millennium Clinical Research

Miami, Florida, United States

Site Status

Optimus U Corporation

Miami, Florida, United States

Site Status

Suncoast Research Group

Miami, Florida, United States

Site Status

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Site Status

University of Miami Hospital

Miami, Florida, United States

Site Status

Dr Gerardo A. Polanco, MD

Miami, Florida, United States

Site Status

Research Institute of South Florida

Miami, Florida, United States

Site Status

Entrust Clinical Research

Miami, Florida, United States

Site Status

Jackson Medical Group Cardiac Care

Miami, Florida, United States

Site Status

Miami Dade Medical Research Institute, LLC

Miami, Florida, United States

Site Status

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

Site Status

Central Florida Cardiology Group

Orlando, Florida, United States

Site Status

Innovation Medical Research Center

Palmetto Bay, Florida, United States

Site Status

DBC Research USA

Pembroke Pines, Florida, United States

Site Status

Progressive Medical Research

Port Orange, Florida, United States

Site Status

My Cardiologist

South Miami, Florida, United States

Site Status

Precision Clinical Research

Sunrise, Florida, United States

Site Status

Genesis Clinical Research, LLC

Tampa, Florida, United States

Site Status

Conquest Research

Winter Park, Florida, United States

Site Status

Centricity Research Columbus Georgia Multispecialty

Columbus, Georgia, United States

Site Status

IACT Health

Columbus, Georgia, United States

Site Status

IACT Health

Rincon, Georgia, United States

Site Status

East-West Medical Research Institute

Honolulu, Hawaii, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Alliance for Multispecialty Research, LLC

Wichita, Kansas, United States

Site Status

Alliance for Multispecialty Research, LLC

Wichita, Kansas, United States

Site Status

Heartland Cardiology, LLC

Wichita, Kansas, United States

Site Status

Centennial Medical Group

Elkridge, Maryland, United States

Site Status

Associates of Cardiology

Silver Spring, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Pioneer Heart Institute

Lincoln, Nebraska, United States

Site Status

Velocity Clinical Research, Norfolk

Norfolk, Nebraska, United States

Site Status

Meridian Clinical Research - 3345 North 107th Street

Omaha, Nebraska, United States

Site Status

Velocity Clinical Research, Omaha

Omaha, Nebraska, United States

Site Status

Sanjay Vohra, MD, F.A.C.C.

Henderson, Nevada, United States

Site Status

Wr-Crcn, Llc.

Las Vegas, Nevada, United States

Site Status

Excel Clinical Research, LLC

Las Vegas, Nevada, United States

Site Status

Las Vegas Clinical Trials

North Las Vegas, Nevada, United States

Site Status

Hassman Research Institute

Berlin, New Jersey, United States

Site Status

Penn Medicine

Somers Point, New Jersey, United States

Site Status

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Site Status

NYU Langone - Center for the Prevention of Cardiovascular Disease

New York, New York, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Rochester General Hospital Infectious Disease

Rochester, New York, United States

Site Status

Rochester General Hospital

Rochester, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Upstate Health Care Center-University Cardiovascular Group of Syracuse

Syracuse, New York, United States

Site Status

SUNY Upstate Medical University Global Health Research Unit

Syracuse, New York, United States

Site Status

M3-Emerging Medical Research, LLC

Durham, North Carolina, United States

Site Status

Carolina Institute for Clinical Research

Fayetteville, North Carolina, United States

Site Status

Monroe Biomedical Research

Monroe, North Carolina, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Aventiv Research Inc.

Columbus, Ohio, United States

Site Status

Centricity Research Columbus Ohio Multispecialty

Columbus, Ohio, United States

Site Status

Columbus Cardiovascular Associates, Inc

Columbus, Ohio, United States

Site Status

Pennsylvania Heart and Vascular Group

Jenkintown, Pennsylvania, United States

Site Status

Main Street Physician's Care

Little River, South Carolina, United States

Site Status

Prolato Clinical Research Center

Houston, Texas, United States

Site Status

DM Clinical Research

Houston, Texas, United States

Site Status

DM Clinical Research

Humble, Texas, United States

Site Status

Cedar Health Research

Irving, Texas, United States

Site Status

Harmony Heart Group

Plano, Texas, United States

Site Status

Mt Olympus Medical Research

Sugar Land, Texas, United States

Site Status

DM Clinical Research

Tomball, Texas, United States

Site Status

Northwest Heart Center

Tomball, Texas, United States

Site Status

Centricity Research Suffolk Primary Care

Suffolk, Virginia, United States

Site Status

Sentara BelleHarbour

Suffolk, Virginia, United States

Site Status

Countries

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United States

References

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Branche A, Mulligan MJ, Maniar A, Puente O, Oladipupo I, Crowther G, Zareba AM, Yi Z, Scully I, Gomme E, Koury K, Kitchin N, Allen PS, Anderson AS, Gurtman A, Lindert K. A Phase 1/2 Randomized Study to Evaluate the Safety, Tolerability, and Immunogenicity of Nucleoside-Modified Messenger RNA Influenza Vaccines in Healthy Adults. Vaccines (Basel). 2025 Apr 3;13(4):383. doi: 10.3390/vaccines13040383.

Reference Type DERIVED
PMID: 40333267 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Sub Study A

View Document

Document Type: Statistical Analysis Plan: Sub Study B

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4781001

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

Other Identifiers

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C4781001

Identifier Type: -

Identifier Source: org_study_id

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