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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 484
- 试验地点
- 67
- 主要终点
- SSA: Percentage of participants reporting local reactions
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
SSA: Observer-blinded, Sponsor Open label SSB: Observer-blinded
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Substudy A: Group 1 to Group 10
- •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
- •Substudy A: Group 11 to Group 14
- •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.
- •Has a body mass index (BMI) between 18 and 35 (inclusive) kg/m2 at the screening visit.
- •Substudy A: Group 1 to Group 10
排除标准
- •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
- •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 85 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.
- •Has a BMI between 18 and 35 (inclusive) kg/m2 at the screening visit.
- •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
- •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.
研究组 & 干预措施
SSB: Group 4
Shingrix, 0, 2 months schedule
干预措施: Shingrix (Biological)
SSA: Group 8
Shingrix, 0, 2 months schedule
干预措施: Shingrix (Biological)
SSA: Group 9
Shingrix, 0, 6 months schedule
干预措施: Shingrix (Biological)
Substudy B (SSB): Group 1
Candidate 2, Dose level 3, lyophilized, 0, 2 months schedule
干预措施: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection (Biological)
SSB: Group 2
Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule
干预措施: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection (Biological)
SSB: Group 3
Candidate 2, Dose level 4, lyophilized, 0, 2 months schedule (saline at month 2)
干预措施: Candidate 2: PF-07921188: VZV modRNA Powder for Suspension for Injection (Biological)
SSA: Group 10
Candidate 1, Dose level 4, lyophilized, 0, 6 months schedule (saline at month 6)
干预措施: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection (Biological)
SubStudy A (SSA): Group 1
Candidate 1, Dose Level 1, lyophilized, 0, 2 months schedule
干预措施: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection (Biological)
SSA: Group 2
Candidate 1, Dose Level 2, lyophilized, 0, 2 months schedule
干预措施: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection (Biological)
SSA: Group 3
Candidate 1, Dose Level 3, lyophilized, 0, 2 months schedule
干预措施: Candidate 1: PF-07915234: VZV modRNA Powder for Suspension for Injection (Biological)
SSA: Group 4
Candidate 1, Dose Level 2, frozen, 0, 2 months schedule
干预措施: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection (Biological)
SSA: Group 5
Candidate 1, Dose Level 2, Frozen, 0, 6 months schedule
干预措施: Candidate 1: PF-07915234: VZV modRNA Suspension for Injection (Biological)
SSA: Group 6
Candidate 2, frozen, 0, 2 months schedule
干预措施: Candidate 2: PF-07921188: VZV modRNA Suspension for Injection (Biological)
SSA: Group 7
Candidate 3, Frozen, 0, 2 months schedule
干预措施: Candidate 3: PF-07921186: VZV modRNA Suspension for Injection (Biological)
结局指标
主要结局
SSA: Percentage of participants reporting local reactions
时间窗: 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
时间窗: 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
时间窗: From Vaccination 1 to 4 weeks after last vaccination
As elicited by investigational site staff
SSA: Percentage of participants reporting serious adverse events
时间窗: 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
时间窗: 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
时间窗: 3 days and 1 week after each vaccination
As measured at the central laboratory
SSA: Percentage of participants with new electrocardiogram (ECG) abnormalities
时间窗: 3 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
时间窗: 3 days and 1 week after each vaccination
as measured at the central laboratory
SSB: Percentage of participants reporting local reactions
时间窗: 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
时间窗: For 7 days after Vaccination 1 and Vaccination 2
Fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, and joint pain, as self-reported in electronic diaries
SSB: Percentage of participants reporting adverse events
时间窗: From Vaccination 1 to 4 weeks after last vaccination
As elicited by investigational site staff
SSB: Percentage of participants reporting serious adverse events
时间窗: 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
时间窗: From Vaccination 1 to 6 months after the last study vaccination
As elicited by investigational site staff
次要结局
- 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)
- 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)
- 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)
- SSB: Geometric mean concentrations (GMCs) of glycoprotein E antibodies in proportion of evaluable immunogenicity participant(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(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(At baseline (before vaccination 1), at 4-weeks after each vaccination and 6-months after last vaccination)