Shingles
Conditions
Brief summary
This study will look at how well Zostavax™ works in preventing shingles in participants ages 50-59 years old.
Interventions
BIOLOGICALZoster Vaccine, Live (Zostavax™)
A single dose 0.65 ml Zostavax™ (Live, attenuated Zoster Vaccine) was administered by subcutaneous injection on Day 1.
BIOLOGICALComparator: Placebo
A single dose of 0.65 ml Placebo (A vaccine stabilizer of Zostavax™ with no live virus) was administered by subcutaneous injection on Day 1.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be between 50 - 59 years of age * No fever on day of vaccination * Females of reproductive potential must be willing to use acceptable form of birth control
Exclusion criteria
* Have received chicken pox or shingles vaccine * Have already had shingles * Have recently had another vaccination * Pregnant or breast feeding. Have participated in another research study in the last 30 days * You are taking certain antiviral drugs * History of allergic reaction to any vaccine component, including gelatin or neomycin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Confirmed Herpes Zoster (HZ) Cases by Vaccination Group | 2 Years | Incidence rate of HZ cases was defined as the number of confirmed HZ cases per 1000 person-years of follow-up following vaccination. Vaccine efficacy for HZ was defined as the relative reduction in incidence rate of HZ in the group that received Zostavax™ compared with the group that received placebo based on the intent-to-treat population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Varicella-zoster Virus (VZV) Antibody Response at 6 Weeks Post Vaccination by Vaccination Group | 6 Weeks | VZV antibody response as measured by Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) in the group that received Zostavax™ compared with the group that received placebo, based on the random subcohort population. |
| Number of Participants Reporting One or More Serious Adverse Experiences by Vaccination Group During the 42-day Postvaccination Follow-up Period | Through 42 days post-vaccination | A serious adverse event is defined as any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an other important medical event based on medical judgement. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zostavax™ Participants randomized to receive a single 0.65 ml subcutaneous injection of Zoster Vaccine, Live (Zostavax™). | 11,211 |
| Placebo Participants randomized to receive a single 0.65 ml subcutaneous injection of placebo. | 11,228 |
| Total | 22,439 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 29 |
| Overall Study | Lost to Follow-up | 353 | 375 |
| Overall Study | Other protocol specified criteria | 13 | 3 |
| Overall Study | Physician Decision | 10 | 7 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Withdrawal by Subject | 263 | 255 |
Baseline characteristics
| Characteristic | Zostavax™ | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 2.8 | 54.8 years STANDARD_DEVIATION 2.8 | 54.8 years STANDARD_DEVIATION 2.8 |
| Sex: Female, Male Female | 6913 Participants | 6972 Participants | 13885 Participants |
| Sex: Female, Male Male | 4298 Participants | 4256 Participants | 8554 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7,228 / 11,094 | 2,183 / 11,116 |
| serious Total, serious adverse events | 243 / 11,094 | 233 / 11,116 |
Outcome results
Primary
Incidence of Confirmed Herpes Zoster (HZ) Cases by Vaccination Group
Incidence rate of HZ cases was defined as the number of confirmed HZ cases per 1000 person-years of follow-up following vaccination. Vaccine efficacy for HZ was defined as the relative reduction in incidence rate of HZ in the group that received Zostavax™ compared with the group that received placebo based on the intent-to-treat population.
Time frame: 2 Years
Population: Intent-to-treat population defined as all participants randomized in the study according to the planned treatment, Zostavax or placebo, they were assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zostavax™ | Incidence of Confirmed Herpes Zoster (HZ) Cases by Vaccination Group | 1.994 number of HZ cases/1000 person-years |
| Placebo | Incidence of Confirmed Herpes Zoster (HZ) Cases by Vaccination Group | 6.596 number of HZ cases/1000 person-years |
Comparison: Vaccine efficacy with respect to HZ was defined as the relative reduction in incidence rate of HZ point estimate (95% CI) calculated as 1 minus the ratio of the estimated incidence rates of HZ in the zoster vaccine group and the placebo group.p-value: <0.00195% CI: [0.541, 0.806]Conditional Exact Method
Secondary
Number of Participants Reporting One or More Serious Adverse Experiences by Vaccination Group During the 42-day Postvaccination Follow-up Period
A serious adverse event is defined as any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an other important medical event based on medical judgement.
Time frame: Through 42 days post-vaccination
Population: All participants who were vaccinated according to actual treatment received (Zostavax or placebo) and had safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zostavax™ | Number of Participants Reporting One or More Serious Adverse Experiences by Vaccination Group During the 42-day Postvaccination Follow-up Period | 69 participants |
| Placebo | Number of Participants Reporting One or More Serious Adverse Experiences by Vaccination Group During the 42-day Postvaccination Follow-up Period | 61 participants |
Comparison: Analysis of proportion of participants reporting one or more serious adverse experiences reported within 42 days postvaccination.95% CI: [0.805, 1.595]
Secondary
Varicella-zoster Virus (VZV) Antibody Response at 6 Weeks Post Vaccination by Vaccination Group
VZV antibody response as measured by Glycoprotein Enzyme-Linked Immunosorbent Assay (gpELISA) in the group that received Zostavax™ compared with the group that received placebo, based on the random subcohort population.
Time frame: 6 Weeks
Population: Random subcohort population included 10% of all randomized participants randomly selected for immunogenicity assay, were vaccinated (according to actual treatment received), had results at prevaccination and at 6 weeks postvaccination. Results from participants with protocol violations that may impact the immunogenicity analysis were excluded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zostavax™ | Varicella-zoster Virus (VZV) Antibody Response at 6 Weeks Post Vaccination by Vaccination Group | 660.0 gpELISA units/mL |
| Placebo | Varicella-zoster Virus (VZV) Antibody Response at 6 Weeks Post Vaccination by Vaccination Group | 293.1 gpELISA units/mL |
p-value: <0.00195% CI: [2.2, 2.4]linear mixed longitudinal analysis model