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

A PHASE 1/2 RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST VARICELLA ZOSTER VIRUS IN HEALTHY INDIVIDUALS

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.

Study Overview

• Status: Terminated
• Conditions: Shingles; Human; Herpes Zoster Infection
• Intervention / Treatment: Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection; Biological: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection; Biological: Candidate 2: PF-07921188: VZV modRNA Suspension for Injection; Biological: Candidate 3: PF-07921186: VZV modRNA Suspension for Injection; Biological: Shingrix; Biological: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection

• Study Type: Interventional
• Enrollment (Actual): 484
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85233
      • Tri-City Cardiology
    • Mesa, Arizona, United States, 85206
      • Aventiv Research Inc.
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • GW Medical Faculty Associates
    • Washington D.C., District of Columbia, United States, 20037
      • GW Vaccine Research Unit
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Proactive Clinical Research,LLC
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
    • Meridian, Idaho, United States, 83642
      • West Valley Cardiology Services
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clinical Trials
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Centennial Medical Group
    • Silver Spring, Maryland, United States, 20910
      • Associates in Cardiology, PA
  • Michigan
    • Detroit, Michigan, United States, 48201
      • C.S. Mott Clinical Research Center (CRC)
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Henry Ford St. John Hospital
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research, Norfolk
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • Nevada
    • Reno, Nevada, United States, 89557
      • University of Nevada School of Medicine - Reno
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • IMA Clinical Research
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10016
      • Tisch Hospital
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare - Wilmington
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health, PLLC (Cardiologist)
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
    • Columbus, Ohio, United States, 43213
      • Columbus Cardiovascular Associates, Inc.
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC
    • San Antonio, Texas, United States, 78229
      • IMA Clinical Research San Antonio
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC dba Flourish Research
    • Tomball, Texas, United States, 77375
      • Dynamed Clinical Research, LP d/b/a DM Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Substudy A: Group 1 to Group 10

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SubStudy A (SSA): Group 1; Candidate 1, Dose Level 1, lyophilized, 0, 2 months schedule	Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 2; Candidate 1, Dose Level 2, lyophilized, 0, 2 months schedule	Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 3; Candidate 1, Dose Level 3, lyophilized, 0, 2 months schedule	Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 4; Candidate 1, Dose Level 2, frozen, 0, 2 months schedule	Biological: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 5; Candidate 1, Dose Level 2, Frozen, 0, 6 months schedule	Biological: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 7; Candidate 3, Frozen, 0, 2 months schedule	Biological: Candidate 3: PF-07921186: VZV modRNA Suspension for Injection; Intramuscular injection
Active Comparator: SSA: Group 8; Shingrix, 0, 2 months schedule	Biological: Shingrix; Intramuscular injection
Active Comparator: SSA: Group 9; Shingrix, 0, 6 months schedule	Biological: Shingrix; Intramuscular injection
Experimental: SSA: Group 6; Candidate 2, frozen, 0, 2 months schedule	Biological: Candidate 2: PF-07921188: VZV modRNA Suspension for Injection; Intramuscular injection
Experimental: SSA: Group 10; Candidate 1, Dose level 4, lyophilized, 0, 6 months schedule (saline at month 6)	Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: Substudy B (SSB): Group 1; Candidate 2, Dose level 3, lyophilized, 0, 2 months schedule	Biological: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: SSB: Group 2; Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule	Biological: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Experimental: SSB: Group 3; Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule (saline at month 2)	Biological: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection; Intramuscular injection
Active Comparator: SSB: Group 4; Shingrix, 0, 2 months schedule	Biological: Shingrix; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Percentage of participants reporting local reactions	Pain at the injection site, redness, and swelling as self-reported in electronic diaries.	For 7 days after Vaccination 1 and Vaccination 2
SSA: Percentage of participants reporting systemic events	Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain, as self-reported in electronic diaries	For 7 days after Vaccination 1 and Vaccination 2
SSA: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Vaccination 1 to 4 weeks after last vaccination
SSA: Percentage of participants reporting serious adverse events	As elicited by investigational site staff	From Vaccination 1 to 6 months after the last study vaccination
SSA: Percentage of participants reporting medically attended adverse event	As elicited by investigational site staff	From Vaccination 1 to 6 months after the last study vaccination
SSB: Percentage of participants reporting local reactions	Pain at the injection site, redness, and swelling as self-reported in electronic diaries.	For 7 days after Vaccination 1 and Vaccination 2
SSB: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Vaccination 1 to 4 weeks after last vaccination
SSB: Percentage of participants reporting serious adverse events	As elicited by investigational site staff	From Vaccination 1 to 6 months after the last study vaccination
SSB: Percentage of participants reporting medically attended adverse events	As elicited by investigational site staff	From Vaccination 1 to 6 months after the last study vaccination
SSA: Percentage of participants with abnormal hematology and chemistry laboratory assessments	As measured at the central laboratory	3 days and 1 week after each vaccination
SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities	ECG abnormalities consistent with probable or possible myocarditis or pericarditis, as judged by a cardiologist	3 days and 1 week after each vaccination
SSA: Percentage of participants with abnormal troponin I laboratory values	as measured at the central laboratory	3 days and 1 week after each vaccination
SSB: Percentage of participants reporting systemic events	Fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, and joint pain, as self-reported in electronic diaries	For 7 days after Vaccination 1 and Vaccination 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participant	As measured at the central laboratory	At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
SSA: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participants	As measured at the central laboratory	At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
SSA: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepoint	As measured at the central laboratory	At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
SSB: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participant	As measured at the central laboratory	At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination
SSB: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participants	As measured at the central laboratory	At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination
SSB: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepoint	As measured at the central laboratory	At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: BioNTech SE
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Actual): September 23, 2025
• Study Completion (Actual): September 23, 2025

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: January 19, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Vaccine; Shingles; Herpes zoster; RNA vaccine; modRNA vaccine
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Herpes Zoster; Chickenpox; Pharmaceutical Preparations; Therapeutics; Dosage Forms; Drug Administration Routes; Drug Therapy; Complex Mixtures; Colloids; Injections; Suspensions
• Other Study ID Numbers: C5031001; NCT05703607 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No