Clinical trial NCT05703607: A Study to Learn About a Modified RNA Vaccine Against Shingles in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Shingles
Herpes Zoster Infection
Human
Keywords: Shingles
Vaccine
RNA vaccine
modRNA vaccine
Herpes zoster
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2023-01-30
Enrollment: 900
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: SSA: Percentage of participants reporting local reactions
timeFrame: For 7 days after Vaccination 1 and Vaccination 2
measure: SSA: Percentage of participants reporting systemic events
timeFrame: For 7 days after Vaccination 1 and Vaccination 2
measure: SSA: Percentage of participants reporting adverse events
timeFrame: From Vaccination 1 to 4 weeks after last vaccination
measure: SSA: Percentage of participants reporting serious adverse events
timeFrame: From Vaccination 1 to 6 months after the last study vaccination
measure: SSA: Percentage of participants reporting medically attended adverse event
timeFrame: From Vaccination 1 to 6 months after the last study vaccination
measure: SSA: Percentage of participants with abnormal hematology and chemistry laboratory assessments
timeFrame: 3 days and 1 week after each vaccination
measure: SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities
timeFrame: 3 days and 1 week after each vaccination
measure: SSA: Percentage of participants with abnormal troponin I laboratory values
timeFrame: 3 days and 1 week after each vaccination
measure: SSB: Percentage of participants reporting local reactions
timeFrame: For 7 days after Vaccination 1 and Vaccination 2
measure: SSB: Percentage of participants reporting systemic events
timeFrame: For 7 days after Vaccination 1 and Vaccination 2
measure: SSB: Percentage of participants reporting adverse events
timeFrame: From Vaccination 1 to 4 weeks after last vaccination
measure: SSB: Percentage of participants reporting serious adverse events
timeFrame: From Vaccination 1 to 6 months after the last study vaccination
measure: SSB: Percentage of participants reporting medically attended adverse events
timeFrame: From Vaccination 1 to 6 months after the last study vaccination
Secondary outcomes:
measure: SSA: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participant
timeFrame: At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
measure: SSA: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participants
timeFrame: At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
measure: SSA: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepoint
timeFrame: At baseline (before vaccination 1), at 1- and 4-weeks after each vaccination and 6-months after last vaccination
measure: SSB: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participant
timeFrame: At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination
measure: SSB: Geometric mean fold rise (GMFR) from before vaccination to each subsequent timepoint in evaluable immunogenicity participants
timeFrame: At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination
measure: SSB: Proportion of evaluable immunogenicity participants with vaccine response in glycoprotein E antibodies from baseline to each subsequent timepoint
timeFrame: At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Tri-City Cardiology
state: Arizona
city: Mesa
country: United States
facility: Aventiv Research Inc.
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Washington
country: United States
facility: GW Medical Faculty Associates
state: District of Columbia
city: Washington
country: United States
facility: GW Vaccine Research Unit
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Proactive Clinical Research,LLC
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research Associates
state: Florida
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Meridian
country: United States
facility: West Valley Cardiology Services
state: Idaho
city: Meridian
country: United States
facility: Solaris Clinical Research
state: Idaho
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lenexa
country: United States
facility: Johnson County Clinical Trials
state: Kansas
city: Columbia
country: United States
facility: Centennial Medical Group
state: Maryland
city: Silver Spring
country: United States
facility: Associates in Cardiology, PA
state: Maryland
city: Detroit
country: United States
facility: C.S. Mott Clinical Research Center (CRC)
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Henry Ford St. John Hospital
state: Michigan
city: Norfolk
country: United States
facility: Velocity Clinical Research, Norfolk
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Reno
country: United States
facility: University of Nevada School of Medicine - Reno
state: Nevada
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Albuquerque
country: United States
facility: IMA Clinical Research
state: New Mexico
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Tisch Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Wilmington
country: United States
facility: Accellacare - Wilmington
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health, PLLC (Cardiologist)
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Columbus
country: United States
facility: Centricity Research Columbus Ohio Multispecialty
state: Ohio
city: Columbus
country: United States
facility: Columbus Cardiovascular Associates, Inc.
state: Ohio
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC dba Flourish Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: San Antonio
country: United States
facility: IMA Clinical Research San Antonio
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research, Martin Diagnostic Clinic
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: