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

Sponsor

Pfizer (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05703607

Collaborator

(none)

900

Enrollment

Arms

76.5

Anticipated Duration (Months)

Study Details

Study Description

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 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 9 groups in the study and will receive 2 doses of vaccine at different intervals.

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.

Condition or Disease	Intervention/Treatment	Phase
Shingles Herpes Zoster Infection Human	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: Selected Vaccine Candidate group (Dose level, Schedule) Biological: Shingrix - SSB	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

900 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

SSA: Observer-blinded, Sponsor Open label SSB: Observer-blinded

Primary Purpose:

Prevention

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

Anticipated Study Start Date :

Jan 23, 2023

Anticipated Primary Completion Date :

Aug 6, 2027

Anticipated Study Completion Date :

Jun 7, 2029

Arms and Interventions

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 6 Candidate 2, frozen, 0, 2 months schedule	Biological: Candidate 2: PF-07921188: 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: Substudy B (SSB): Group 1 Selected Vaccine candidate/dose-level/dosing schedule	Biological: Selected Vaccine Candidate group (Dose level, Schedule) Intramuscular injection Other Names: Intramuscular injection
Experimental: SSB: Group 2 Shingrix	Biological: Shingrix - SSB Intramuscular injection Other Names: Shingrix group

Outcome Measures

Primary Outcome Measures

SSA: Percentage of participants reporting local reactions [For 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 events [For 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 events [From Vaccination 1 to 4 weeks after last vaccination]
As elicited by investigational site staff
SSA: Percentage of participants reporting serious adverse events [From Vaccination 1 to 6 months after the last study vaccination]
As elicited by investigational site staff
SSA: Percentage of participants reporting medically attended adverse event [From 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 assessments [2 days and 1 week after each vaccination]
As measured at the central laboratory
SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities [2 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 values [2 days after each vaccination]
as measured at the central laboratory
SSB: Percentage of participants reporting local reactions [For 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 events [For 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
SSB: Percentage of participants reporting adverse events [From Vaccination 1 to 4 weeks after last vaccination]
As elicited by investigational site staff
SSB: Percentage of participants reporting serious adverse events [From Vaccination 1 to 6 months after the last study vaccination]
As elicited by investigational site staff
SSB: Percentage of participants reporting medically attended adverse events [From Vaccination 1 to 6 months after the last study vaccination]
As elicited by investigational site staff
Overall study: Percentage of participants from both substudies reporting local reactions [For up to 7 days following each vaccination]
Pain at the injection site, redness, and swelling as self-reported in electronic diaries.
Overall study: Percentage of participants from both substudies reporting systemic events [For up to 7 days following 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
Overall study: Percentage of participants from both substudies reporting adverse events [From vaccination 1 to 4 weeks after vaccination 2]
As elicited by investigational site staff
Overall study: Percentage of participants from both substudies reporting serious adverse events [From vaccination 1 to 6 months after the last study vaccination]
As elicited by investigational site staff
Overall study: Percentage of participants from both substudies reporting medically attended adverse events [From vaccination 1 to 6 months after the last study vaccination]
As elicited by investigational site staff

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Substudy A

Inclusion Criteria:

Male or female participants 50 through 69 years of age (inclusive) at the time of consent.
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.
Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol

Exclusion Criteria:

History of HZ (shingles).
History of Guillain-Barré syndrome.
Known infection with HIV, HCV, or HBV.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
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.
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.
Women who are pregnant or breastfeeding.
Prior history of heart disease (eg, heart failure, recent coronary artery disease, cardiomyopathies, pericarditis/myocarditis).
Previous vaccination with any varicella or HZ vaccine.
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.
Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
Any participant who has received or plans to receive an RNA vaccine 28 days prior to Vaccination 1.
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.
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.
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.
Participation or planned participation in strenuous or endurance exercise within 7 days before or after each study intervention administration.
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:

Male or female participants 50 through 69 years of age (inclusive) at the time of consent.
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.
Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

History of HZ (shingles).
History of Guillain-Barré syndrome.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
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.
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.
Women who are pregnant or breastfeeding.
Prior history of heart disease (eg, heart failure, recent coronary artery disease, cardiomyopathies, pericarditis, or myocarditis).
Previous vaccination with any varicella or HZ vaccine.
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.
Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
Any participant who has received or plans to receive an RNA vaccine 28 days prior to Vaccination 1.
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.
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.