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

Study Overview
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Brief Summary
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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 11 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.

Official Title
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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

Conditions
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Shingles, Herpes Zoster Infection, Human

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SubStudy A (SSA): Group 1<br>Candidate 1, Dose Level 1, lyophilized, 0, 2 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 2<br>Candidate 1, Dose Level 2, lyophilized, 0, 2 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 3<br>Candidate 1, Dose Level 3, lyophilized, 0, 2 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 4<br>Candidate 1, Dose Level 2, frozen, 0, 2 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 5<br>Candidate 1, Dose Level 2, Frozen, 0, 6 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA- Group 6<br>Candidate 2, frozen, 0, 2 months schedule | Biological: Candidate 2: PF-07921188: VZV modRNA Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 7<br>Candidate 3, Frozen, 0, 2 months schedule | Biological: Candidate 3: PF-07921186: VZV modRNA Suspension for Injection<br>* Intramuscular injection<br>|
| Active Comparator: SSA: Group 8<br>Shingrix, 0, 2 months schedule | Biological: Shingrix<br>* Intramuscular injection<br>|
| Active Comparator: SSA: Group 9<br>Shingrix, 0, 6 months schedule | Biological: Shingrix<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 10<br>Candidate 1, Dose level 4, lyophilized, 0, 6 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: SSA: Group 11<br>Candidate 1, Dose level 4, lyophilized, 0, 2 months schedule | Biological: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection<br>* Intramuscular injection<br>|
| Experimental: Substudy B (SSB): Group 1<br>Selected Vaccine candidate/dose-level/dosing schedule | Biological: Selected Vaccine Candidate group (Dose level, Schedule)<br>* Intramuscular injection<br>* Other names: Intramuscular injection;|
| Active Comparator: SSB: Group 2<br>Shingrix | Biological: Shingrix - SSB<br>* Intramuscular injection<br>* Other names: Shingrix group;|

What is the study measuring?
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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 | 
| SSA: Percentage of participants with abnormal hematology and chemistry laboratory assessments | As measured at the central laboratory | 2 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 | 2 days and 1 week after each vaccination | 
| SSA: Percentage of participants with abnormal troponin I laboratory values | as measured at the central laboratory | 2 days after each 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 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 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 1- and 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 1- and 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 1- and 4-weeks after each vaccination and 6-months after last vaccination | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shingles, Vaccine, RNA vaccine, modRNA vaccine, Herpes zoster