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A Study to Learn About a Modified RNA Vaccine Against Shingles in Healthy Adults

Phase 2
Active, not recruiting
Conditions
Human
Herpes Zoster Infection
Shingles
Interventions
Registration Number
NCT05703607
Lead Sponsor
Pfizer
Brief Summary

The purpose of this clinical study is to learn about the safety, extent of the side effects (reaction to vaccine), and immune response (your immune system's reaction) of the study vaccine called Varicella Zoster Virus modRNA (VZV modRNA). We are seeking for healthy participants 50 through 85 years of age.

This study will be conducted in 2 substudies: Substudy A (Phase 1) and Substudy B (Phase 2).

Substudy A:

This substudy is the Phase 1 portion of the study. In this substudy, participants will receive 1 of 3 VZV modRNA vaccine candidates (different construct, different dose levels and different formulation \[frozen or freeze dry powder\]) or the approved shingles vaccine intramuscularly.

Participants will be assigned in 1 of 10 groups in the study. Vaccination will be given either as a 2-dose series using one of two dosing schedules (either 2-months apart or 6-months apart), or (in one of the groups), as a single VZV modRNA vaccine at the first vaccination visit and saline at the second vaccination visit.

Participants will take part in this study for 8 to 12 months depending on the group they are assigned to. Some group(s) will continue into persistence-of-immunity (overtime assessment of effect of vaccine) portion of the study. Those participants assigned to these selected groups will be involved in the study for up to 5 years.

Substudy B:

This substudy is the Phase 2 portion of the study. In this part of the study, participants will receive either VZV modRNA vaccine at selected dose level/schedule/formulation or approved shingles vaccine. This selection was determined from data collected in Substudy A.

Participants will be involved in this study for up to 5 years.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
900
Inclusion Criteria
  1. Male or female participants 50 through 69 years of age (inclusive) at the time of consent.
  2. Healthy participants who are determined by clinical assessment, including medical history and clinical judgment of the investigator, to be eligible for inclusion in the study. Note: Known infection with HIV, HCV or HBV is an exclusion in Substudy A.
  3. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
  4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol

Substudy A: Group 11 to Group 14

Inclusion Criteria:

  1. Male or female participants 50 through 69 years of age (inclusive) at the time of consent.
  2. Healthy participants who are determined by clinical assessment, including medical history and clinical judgment of the investigator, to be eligible for inclusion in the study. Note: Known infection with HIV, HCV or HBV is an exclusion in Substudy A.
  3. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
  4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
  5. Has a body mass index (BMI) between 18 and 35 (inclusive) kg/m2 at the screening visit.

Substudy A: Group 1 to Group 10

Exclusion Criteria
  1. History of HZ (shingles).
  2. History of Guillain-Barré syndrome.
  3. Known infection with HIV, HCV, or HBV.
  4. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
  5. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  7. 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.
  8. Women who are pregnant or breastfeeding.
  9. Prior history of heart disease (eg, heart failure, recent coronary artery disease, cardiomyopathies, pericarditis/myocarditis).
  10. Previous vaccination with any varicella or HZ vaccine.
  11. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  12. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
  13. Any participant who has received or plans to receive an RNA vaccine 28 days prior to Vaccination 1.
  14. Participation in other interventional studies within 28 days prior to study entry or anticipated involvement through and including 6 months after the last dose of study intervention. Participation in observational studies is permitted.
  15. Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality; or any abnormal bilirubin or troponin I value.
  16. Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis/pericarditis or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
  17. Participation or planned participation in strenuous or endurance exercise within 7 days before or after each study intervention administration.
  18. 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.

SubStudy B:

Inclusion Criteria:

  1. Male or female participants 50 through 85 years of age (inclusive) at the time of consent.
  2. Healthy participants who are determined by clinical assessment, including medical history and clinical judgment of the investigator, to be eligible for inclusion in the study.
  3. Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
  4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
  5. Has a BMI between 18 and 35 (inclusive) kg/m2 at the screening visit.

Exclusion Criteria:

  1. History of HZ (shingles).
  2. History of Guillain-Barré syndrome.
  3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
  4. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
  5. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  6. 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.
  7. Women who are pregnant or breastfeeding.
  8. Prior history of heart disease (eg, heart failure, recent coronary artery disease, cardiomyopathies, pericarditis, or myocarditis).
  9. Previous vaccination with any varicella or HZ vaccine.
  10. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
  11. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
  12. Any participant who has received or plans to receive an RNA vaccine 28 days prior to Vaccination 1.
  13. Participation in other interventional studies within 28 days prior to study entry or anticipated involvement through and including 6 months after the last dose of study intervention is prohibited. Participation in observational studies is permitted.
  14. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
SSA: Group 8ShingrixShingrix, 0, 2 months schedule
SSA: Group 9ShingrixShingrix, 0, 6 months schedule
SSB: Group 4ShingrixShingrix, 0, 2 months schedule
Primary Outcome Measures
NameTimeMethod
SSA: Percentage of participants reporting local reactionsFor 7 days after Vaccination 1 and Vaccination 2

Pain at the injection site, redness, and swelling as self-reported in electronic diaries.

SSA: Percentage of participants reporting systemic eventsFor 7 days after Vaccination 1 and Vaccination 2

Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries

SSA: Percentage of participants reporting adverse eventsFrom Vaccination 1 to 4 weeks after last vaccination

As elicited by investigational site staff

SSA: Percentage of participants reporting serious adverse eventsFrom Vaccination 1 to 6 months after the last study vaccination

As elicited by investigational site staff

SSA: Percentage of participants reporting medically attended adverse eventFrom Vaccination 1 to 6 months after the last study vaccination

As elicited by investigational site staff

SSA: Percentage of participants with abnormal hematology and chemistry laboratory assessments3 days and 1 week after each vaccination

As measured at the central laboratory

SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities3 days and 1 week after each vaccination

ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist

SSA: Percentage of participants with abnormal troponin I laboratory values3 days and 1 week after each vaccination

as measured at the central laboratory

SSB: Percentage of participants reporting local reactionsFor 7 days after Vaccination 1 and Vaccination 2

Pain at the injection site, redness, and swelling as self-reported in electronic diaries.

SSB: Percentage of participants reporting systemic eventsFor 7 days after Vaccination 1 and Vaccination 2

Fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, and joint pain, as self-reported in electronic diaries

SSB: Percentage of participants reporting adverse eventsFrom Vaccination 1 to 4 weeks after last vaccination

As elicited by investigational site staff

SSB: Percentage of participants reporting serious adverse eventsFrom Vaccination 1 to 6 months after the last study vaccination

As elicited by investigational site staff

SSB: Percentage of participants reporting medically attended adverse eventsFrom Vaccination 1 to 6 months after the last study vaccination

As elicited by investigational site staff

Secondary Outcome Measures
NameTimeMethod
SSA: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participantAt baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

SSA: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participantsAt baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

SSA: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepointAt baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

SSB: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participantAt baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

SSB: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participantsAt baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

SSB: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepointAt baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination

As measured at the central laboratory

Trial Locations

Locations (35)

CTI Clinical Research Center

🇺🇸

Cincinnati, Ohio, United States

DM Clinical Research, Martin Diagnostic Clinic

🇺🇸

Tomball, Texas, United States

Tri-City Cardiology

🇺🇸

Gilbert, Arizona, United States

Stanford University Medical Center

🇺🇸

Palo Alto, California, United States

Quality Clinical Research

🇺🇸

Omaha, Nebraska, United States

Proactive Clinical Research,LLC

🇺🇸

Fort Lauderdale, Florida, United States

South Jersey Infectious Disease

🇺🇸

Somers Point, New Jersey, United States

Rochester Clinical Research, LLC

🇺🇸

Rochester, New York, United States

Accellacare - Wilmington

🇺🇸

Wilmington, North Carolina, United States

Aventiv Research Inc.

🇺🇸

Mesa, Arizona, United States

Diablo Clinical Research, Inc.

🇺🇸

Walnut Creek, California, United States

Acevedo Clinical Research Associates

🇺🇸

Miami, Florida, United States

East-West Medical Research Institute

🇺🇸

Honolulu, Hawaii, United States

West Valley Cardiology Services

🇺🇸

Meridian, Idaho, United States

Solaris Clinical Research

🇺🇸

Meridian, Idaho, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Johnson County Clinical Trials

🇺🇸

Lenexa, Kansas, United States

Centennial Medical Group

🇺🇸

Columbia, Maryland, United States

Associates in Cardiology, PA

🇺🇸

Silver Spring, Maryland, United States

C.S. Mott Clinical Research Center (CRC)

🇺🇸

Detroit, Michigan, United States

Velocity Clinical Research, Norfolk

🇺🇸

Norfolk, Nebraska, United States

University of Nevada School of Medicine - Reno

🇺🇸

Reno, Nevada, United States

Henry Ford St. John Hospital

🇺🇸

Grosse Pointe Woods, Michigan, United States

GW Vaccine Research Unit

🇺🇸

Washington, District of Columbia, United States

GW Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

IMA Clinical Research

🇺🇸

Albuquerque, New Mexico, United States

Tisch Hospital

🇺🇸

New York, New York, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

NYU Langone Health

🇺🇸

New York, New York, United States

Wilmington Health, PLLC (Cardiologist)

🇺🇸

Wilmington, North Carolina, United States

Centricity Research Columbus Ohio Multispecialty

🇺🇸

Columbus, Ohio, United States

Columbus Cardiovascular Associates, Inc.

🇺🇸

Columbus, Ohio, United States

Clinical Trials of Texas, LLC dba Flourish Research

🇺🇸

San Antonio, Texas, United States

Clinical Trials of Texas, LLC

🇺🇸

San Antonio, Texas, United States

IMA Clinical Research San Antonio

🇺🇸

San Antonio, Texas, United States

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