Herpes Zoster, Varicella-zoster Vaccine
Conditions
Keywords
Shingles, Vaccine
Brief summary
This study was conducted to obtain safety and immunogenicity data after a booster dose of Zoster Vaccine, Live administered ≥10 years following an initial dose. This information was compared to similar information obtained after Zoster Vaccine, Live administration to age-matched and younger participants who received their first dose of Zoster Vaccine, Live. The study was designed to determine: 1) whether a booster dose of Zoster Vaccine, Live in participants ≥70 years of age induces an antibody response that is noninferior to that of a first dose of Zoster Vaccine, Live in participants matched for age; 2) whether a booster dose of Zoster Vaccine, Live induces an acceptable rise in the level of varicella-zoster virus (VZV) antibodies.
Detailed description
All participants were followed for one year after completion of the 42-day post-vaccination period while Groups 1 and 2 were followed for a total of three years.
Interventions
BIOLOGICALZoster Vaccine, Live
Single approximately 0.65-mL subcutaneous injection of Zoster Vaccine, Live on Day 1 of the study
Sponsors
University of Colorado, Denver
Duke University
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* All Groups: * Must not have a fever of ≥100.4° F on the day of vaccination * Any underlying chronic illness must be in stable condition * History of varicella or residence in a VZV-endemic area for ≥30 years * Group 1: * 70 years of age or older * Took part in the Shingles Prevention Study (SPS) (V211-004, NCT00007501) and received a single dose of Zoster Vaccine, Live ≥10 years prior to enrollment in this study * Group 2: * 70 years of age or older * Group 3: * 60 to 69 years of age * Group 4: * 50 to 59 years of age
Exclusion criteria
* All Groups: * History of hypersensitivity reaction to any vaccine component or an anaphylactic/anaphylactoid reaction to neomycin * Prior history of herpes zoster * Pregnant or breast-feeding, or expecting to conceive within the duration of the study * Has been treated with immunoglobulin or any blood products, other than autologous (self-donated) blood transfusion, in the 5 months prior to vaccination * Received any other vaccine within 4 weeks prevaccination * On immunosuppressive therapy * Has known or suspected immune dysfunction * Is taking any non-topical antiviral therapy with activity against herpesviruses, including, but not limited to acyclovir, famciclovir, valacyclovir, and ganciclovir. * Groups 2, 3, and 4: * Has previously received any varicella or zoster vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV) | Day 1 (Baseline) and Week 6 postvaccination | VZV antibody titers were determined by glycoprotein enzyme-linked immunosorbent assay (gpELISA) |
| Geometric Mean Fold Rise (GMFR) From Day 1 (Baseline) to Week 6 Postvaccination in VZV Antibody Titers | Day 1 (Baseline) and Week 6 postvaccination | VZV antibody titers were determined by gpELISA. The GMFR measures the rise in VZV antibodies from Day 1 (Baseline) to Week 6 postvaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Adverse Experiences | Up to 42 days postvaccination | An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse experience. A serious adverse experience is any AE that results in death, is life threatening, results in persistent disability/incapacity, results in or prolongs existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is another important medical event that may jeopardize the participant and may require medical or surgical intervention. Vaccine-related AEs were those assessed by the investigator as definitely, probably, or possibly related to vaccine administration. This outcome measure applies only to AEs collected after vaccination in Part 1 of the current study. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Booster Dose Participants ≥70 Years of Age Herpes zoster history-negative participants ≥70 years of age who received Zoster Vaccine, Live approximately 10 years prior in the Shingles Prevention Study V211-004 (NCT00007501). Participants received a single Zoster Vaccine, Live vaccination on Day 1. | 201 |
| Group 2: First Dose Participants ≥70 Years of Age Herpes zoster history-negative participants ≥70 years of age who have never received Zoster Vaccine, Live and are matched to Group 1 participants by age. Participants received a single Zoster Vaccine, Live vaccination on Day 1. | 199 |
| Group 3: First Dose Participants ≥60 and <70 Years of Age Herpes zoster history-negative participants ≥60 and \<70 years of age who have never received Zoster Vaccine, Live. Participants received a single Zoster Vaccine, Live vaccination on Day 1. | 100 |
| Group 4: First Dose Participants ≥50 and <60 Years of Age Herpes zoster history-negative participants ≥50 and \<60 years of age who have never received Zoster Vaccine, Live. Participants received a single Zoster Vaccine, Live vaccination on Day 1. | 100 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Day 1 to Week 52 (1 Year) | Death | 2 | 1 | 0 | 0 |
| Part 1: Day 1 to Week 52 (1 Year) | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Part 1: Day 1 to Week 52 (1 Year) | Withdrawal by Subject | 0 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1: Booster Dose Participants ≥70 Years of Age | Group 2: First Dose Participants ≥70 Years of Age | Group 3: First Dose Participants ≥60 and <70 Years of Age | Group 4: First Dose Participants ≥50 and <60 Years of Age | Total |
|---|---|---|---|---|---|
| Age, Continuous | 77.1 years STANDARD_DEVIATION 4.5 | 76.3 years STANDARD_DEVIATION 5.1 | 64.1 years STANDARD_DEVIATION 3.1 | 55.5 years STANDARD_DEVIATION 2.8 | 71.1 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 107 Participants | 94 Participants | 65 Participants | 77 Participants | 343 Participants |
| Sex: Female, Male Male | 94 Participants | 105 Participants | 35 Participants | 23 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 76 / 201 | 58 / 199 | 61 / 100 | 62 / 100 |
| serious Total, serious adverse events | 29 / 201 | 29 / 199 | 6 / 100 | 2 / 100 |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) From Day 1 (Baseline) to Week 6 Postvaccination in VZV Antibody Titers
VZV antibody titers were determined by gpELISA. The GMFR measures the rise in VZV antibodies from Day 1 (Baseline) to Week 6 postvaccination.
Time frame: Day 1 (Baseline) and Week 6 postvaccination
Population: Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of VZV antibody response, who developed varicella or herpes zoster rashes before a blood sample was taken, or who reported exposure to varicella or herpes zoster. The planned analysis included Group 1 only.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1: Booster Dose Participants ≥70 Years of Age | Geometric Mean Fold Rise (GMFR) From Day 1 (Baseline) to Week 6 Postvaccination in VZV Antibody Titers | 1.5 Fold Rise |
Comparison: A booster dose induces a statistically acceptable VZV antibody response if the lower bound of the 95% confidence interval is \>1.0.p-value: <0.00195% CI: [1.44, 1.66]Longitudinal regression model
Primary
Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV)
VZV antibody titers were determined by glycoprotein enzyme-linked immunosorbent assay (gpELISA)
Time frame: Day 1 (Baseline) and Week 6 postvaccination
Population: Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of VZV antibody response, who developed varicella or herpes zoster rashes before a blood sample was taken, or who reported exposure to varicella or herpes zoster. The planned analysis included Group 1 versus Group 2 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1: Booster Dose Participants ≥70 Years of Age | Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV) | Week 6 postvaccination, n=198, 195 | 389.1 gpELISA Units/mL |
| Group 1: Booster Dose Participants ≥70 Years of Age | Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV) | Day 1 (Baseline), n=201, 199 | 248.0 gpELISA Units/mL |
| Group 2: First Dose Participants ≥70 Years of Age | Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV) | Day 1 (Baseline), n=201, 199 | 254.2 gpELISA Units/mL |
| Group 2: First Dose Participants ≥70 Years of Age | Geometric Mean Titer (GMT) of the Antibody Responses to Varicella-Zoster Virus (VZV) | Week 6 postvaccination, n=198, 195 | 368.6 gpELISA Units/mL |
Comparison: Week 6 analysisp-value: <0.00195% CI: [0.97, 1.15]Longitudinal regression model
Secondary
Number of Participants Reporting One or More Adverse Experiences
An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse experience. A serious adverse experience is any AE that results in death, is life threatening, results in persistent disability/incapacity, results in or prolongs existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is another important medical event that may jeopardize the participant and may require medical or surgical intervention. Vaccine-related AEs were those assessed by the investigator as definitely, probably, or possibly related to vaccine administration. This outcome measure applies only to AEs collected after vaccination in Part 1 of the current study.
Time frame: Up to 42 days postvaccination
Population: Analysis included all vaccinated participants who had any safety follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Booster Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Vaccine-related Serious Adverse Event | 0 Participants |
| Group 1: Booster Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Non-Injection-site Adverse Event | 66 Participants |
| Group 1: Booster Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Serious Adverse Event | 3 Participants |
| Group 1: Booster Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Injection-site Adverse Event | 68 Participants |
| Group 1: Booster Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Any Adverse Event | 104 Participants |
| Group 2: First Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Serious Adverse Event | 5 Participants |
| Group 2: First Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Vaccine-related Serious Adverse Event | 0 Participants |
| Group 2: First Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Any Adverse Event | 95 Participants |
| Group 2: First Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Non-Injection-site Adverse Event | 57 Participants |
| Group 2: First Dose Participants ≥70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Injection-site Adverse Event | 61 Participants |
| Group 3: First Dose Participants ≥60 and <70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Injection-site Adverse Event | 56 Participants |
| Group 3: First Dose Participants ≥60 and <70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Any Adverse Event | 72 Participants |
| Group 3: First Dose Participants ≥60 and <70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Non-Injection-site Adverse Event | 34 Participants |
| Group 3: First Dose Participants ≥60 and <70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Vaccine-related Serious Adverse Event | 0 Participants |
| Group 3: First Dose Participants ≥60 and <70 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Serious Adverse Event | 1 Participants |
| Group 4: First Dose Participants ≥50 and <60 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Vaccine-related Serious Adverse Event | 0 Participants |
| Group 4: First Dose Participants ≥50 and <60 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Any Adverse Event | 72 Participants |
| Group 4: First Dose Participants ≥50 and <60 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Non-Injection-site Adverse Event | 38 Participants |
| Group 4: First Dose Participants ≥50 and <60 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Serious Adverse Event | 0 Participants |
| Group 4: First Dose Participants ≥50 and <60 Years of Age | Number of Participants Reporting One or More Adverse Experiences | Injection-site Adverse Event | 57 Participants |