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

Shingles Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05703607
• Other study ID #: C5031001
• Status: Recruiting
• Phase: Phase 2
• Start date: January 25, 2023
• Est. completion date: June 22, 2030

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 who are between 50 and 69 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 14 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 will be determined from Substudy A.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: June 22, 2030
• Est. primary completion date: December 20, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 69 Years

Eligibility

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 A: Group 11 to Group 14 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 (including use of anticoagulant medications within 7 days prior to enrollment) that would contraindicate IM injection or imply treatment or prophylaxis of known cardiac or valvular disease.

Note: The use of =325 mg of aspirin per day as prophylaxis is permitted, but the use of other platelet aggregation inhibitors, thrombin inhibitors, Factor Xa inhibitors, or warfarin derivatives from 7 days prior to enrollment through conclusion of study participation is exclusionary.

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. This includes a history of alcohol or drug abuse as determined by the investigator.

8. Women who are pregnant or breastfeeding.

9. Prior history of heart disease (eg, heart failure, coronary artery disease, cardiomyopathies, pericarditis/myocarditis, or uncontrolled hypertension).

10. Participant with a history of autoimmune disease including, but not limited to, systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, multiple sclerosis, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, temporal arteritis, psoriasis, and/or insulin dependent diabetes mellitus.

11. Previous vaccination with any varicella or HZ vaccine.

12. 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. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

13. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.

Note: Nonimmunosuppressive monoclonal antibodies are permitted.

14. Any participant who has received or plans to receive an RNA vaccine 28 days prior to Vaccination 1

15. 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.

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study.

16. 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.

Note: Any abnormal bilirubin or troponin I value above the ULN reference range is exclusionary. Participants with any stable Grade 1 abnormalities (according to the toxicity grading scale), except bilirubin and troponin I, may be considered eligible at the discretion of the investigator. (Note: A "stable" Grade 1 laboratory abnormality is defined as a report of Grade 1 on an initial blood sample that remains less than or equal to Grade 1 upon repeat testing on a second sample from the same participant during the screening period (prior to Visit 1). Please refer to the laboratory normal ranges (provided separately in the central laboratory manual) for grading scales for abnormalities.

17. 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. Participants with a screening 12-lead ECG that shows an average QTcF interval >450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias should be excluded from study participation.

18. Participation or planned participation in strenuous or endurance exercise within 7 days before or after each study intervention administration.

19. 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 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.

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.

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.

Related Conditions & MeSH terms

• Herpes Zoster
• Human
• Shingles

Intervention

Biological:
• Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection
Intramuscular injection
• Candidate 1: PF-07915234: VZV modRNA Suspension for Injection
Intramuscular injection
• Candidate 2: PF-07921188: VZV modRNA Suspension for Injection
Intramuscular injection
• Candidate 3: PF-07921186: VZV modRNA Suspension for Injection
Intramuscular injection
• Shingrix
Intramuscular injection
• Selected Vaccine Candidate group (Dose level, Schedule)
Intramuscular injection
• Shingrix - SSB
Intramuscular injection
• Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection
Intramuscular injection

Locations

Country	Name	City	State
United States	IMA Clinical Research	Albuquerque	New Mexico
United States	CTI Clinical Research Center	Cincinnati	Ohio
United States	Centennial Medical Group	Columbia	Maryland
United States	Aventiv Research Inc	Columbus	Ohio
United States	Centricity Research Columbus Ohio Multispecialty	Columbus	Ohio
United States	Columbus Cardiovascular Associates, Inc.	Columbus	Ohio
United States	C.S. Mott Clinical Research Center (CRC)	Detroit	Michigan
United States	Centennial Medical Group	Elkridge	Maryland
United States	Proactive Clinical Research,LLC	Fort Lauderdale	Florida
United States	Tri-City Cardiology	Gilbert	Arizona
United States	Ascension St. John Hospital	Grosse Pointe Woods	Michigan
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	University of Iowa	Iowa City	Iowa
United States	Johnson County Clinical Trials	Lenexa	Kansas
United States	Solaris Clinical Research	Meridian	Idaho
United States	West Valley Cardiology Services	Meridian	Idaho
United States	Aventiv Research Inc.	Mesa	Arizona
United States	Acevedo Clinical Research Associates	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	NYU Langone Health	New York	New York
United States	Tisch Hospital	New York	New York
United States	Velocity Clinical Research, Norfolk	Norfolk	Nebraska
United States	Quality Clinical Research	Omaha	Nebraska
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Nevada School of Medicine - Reno	Reno	Nevada
United States	Rochester Clinical Research, LLC	Rochester	New York
United States	Clinical Trials of Texas, LLC	San Antonio	Texas
United States	IMA Clinical Research San Antonio	San Antonio	Texas
United States	Associates in Cardiology, PA	Silver Spring	Maryland
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Cardiology Associates of Fairfield County	Stamford	Connecticut
United States	Stamford Therapeutics Consortium	Stamford	Connecticut
United States	DM Clinical Research	Tomball	Texas
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	GW Medical Faculty Associates	Washington	District of Columbia
United States	GW Vaccine Research Unit	Washington	District of Columbia
United States	Accellacare - Wilmington	Wilmington	North Carolina
United States	Wilmington Health, PLLC (Cardiologist)	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	SSA: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Vaccination 1 to 4 weeks after last vaccination
Primary	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
Primary	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
Primary	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
Primary	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
Primary	SSA: Percentage of participants with abnormal troponin I laboratory values	as measured at the central laboratory	3 days and 1 week after each vaccination
Primary	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
Primary	SSB: 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
Primary	SSB: Percentage of participants reporting adverse events	As elicited by investigational site staff	From Vaccination 1 to 4 weeks after last vaccination
Primary	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
Primary	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
Primary	Overall study: Percentage of participants from both substudies reporting local reactions	Pain at the injection site, redness, and swelling as self-reported in electronic diaries.	For up to 7 days following each vaccination
Primary	Overall study: Percentage of participants from both substudies 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 up to 7 days following each vaccination
Primary	Overall study: Percentage of participants from both substudies reporting adverse events	As elicited by investigational site staff	From vaccination 1 to 4 weeks after vaccination 2
Primary	Overall study: Percentage of participants from both substudies reporting serious adverse events	As elicited by investigational site staff	From vaccination 1 to 6 months after the last study vaccination
Primary	Overall study: Percentage of participants from both substudies reporting medically attended adverse events	As elicited by investigational site staff	From vaccination 1 to 6 months after the last study vaccination
Secondary	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
Secondary	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
Secondary	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
Secondary	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 1- and 4-weeks after each vaccination and 6-months after last vaccination
Secondary	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 1- and 4-weeks after each vaccination and 6-months after last vaccination
Secondary	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 1- and 4-weeks after each vaccination and 6-months after last vaccination
Secondary	Overall study: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in evaluable immunogenicity participants in both substudies	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
Secondary	Overall study: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participants from both substudies	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
Secondary	Overall study: Proportion of evaluable immunogenicity participants from both substudies 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

External Links

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