Herpes Zoster, Shingles
Conditions
Brief summary
This study will determine whether ZOSTAVAX™ made with an alternative manufacturing process \[ZOSTAVAX™ (AMP)\] is well tolerated and immunogenic, and has a comparable immune response to ZOSTAVAX™.
Interventions
BIOLOGICALZoster Vaccine, Live (AMP)
One approximately 0.65-mL injection subcutaneously on Day 1
BIOLOGICALZoster Vaccine, Live
One approximately 0.65-mL injection subcutaneously 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 No maximum
Healthy volunteers
Yes
Inclusion criteria
* No fever on day of vaccination * History of varicella or residence in a VZV-endemic area for ≥30 years * Females of reproductive potential must have a negative pregnancy test and must agree to use acceptable methods of birth control
Exclusion criteria
* History of hypersensitivity reaction to any vaccine component * Prior receipt of any varicella or zoster vaccine * Prior history of herpes zoster * Have recently had another vaccination * Pregnant or breastfeeding * Use of immunosuppressive therapy * Known or suspected immune dysfunction * Concomitant antiviral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody | Day 1 and Week 6 postvaccination | VZV antibody titers were determined by glycoprotein enzyme-linked immunosorbent assay (gpELISA) |
| Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers | Day 1 (Baseline) to Week 6 postvaccination | VZV antibody titers were determined by gpELISA. The GMFR reports the geometric mean of the ratio of individual participant VZV antibody titers at Week 6 / Day 1 (Baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Adverse Experiences (AEs) | Day 1 to Day 42 postvaccination | An 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. |
| Number of Participants With One or More Serious Adverse Experience (SAE) Day 1 to 42 Postvaccination | Day 1 to Day 42 postvaccination | An SAE 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 |
| Number of Participants With One or More Serious Adverse Experience Day 1 to 182 Postvaccination | Day 1 to Day 182 postvaccination | An SAE 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
Pre-assignment details
One participant in the ZOSTAVAX™ (AMP) group was randomized but not vaccinated, making the number of participants vaccinated in this group 331
Participants by arm
| Arm | Count |
|---|---|
| ZOSTAVAX™ (AMP) Zoster Vaccine, Live (AMP) : One approximately 0.65-mL injection subcutaneously on Day 1 | 332 |
| ZOSTAVAX™ Zoster Vaccine, Live : One approximately 0.65-mL injection subcutaneously on Day 1 | 166 |
| Total | 498 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Day 1 Through Day 42 Follow-up | Lost to Follow-up | 1 | 0 |
| Day 1 Through Day 42 Follow-up | Physician Decision | 1 | 0 |
| Day 1 Through Day 42 Follow-up | Withdrawal by Subject | 1 | 0 |
| Day 43 Through Day 182 Follow-up | Death | 0 | 1 |
| Day 43 Through Day 182 Follow-up | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | ZOSTAVAX™ (AMP) | ZOSTAVAX™ | Total |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 7.1 | 62.4 years STANDARD_DEVIATION 7 | 62.8 years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 196 Participants | 99 Participants | 295 Participants |
| Sex: Female, Male Male | 136 Participants | 67 Participants | 203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 186 / 330 | 85 / 166 |
| serious Total, serious adverse events | 4 / 330 | 8 / 166 |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers
VZV antibody titers were determined by gpELISA. The GMFR reports the geometric mean of the ratio of individual participant VZV antibody titers at Week 6 / Day 1 (Baseline).
Time frame: Day 1 (Baseline) to Week 6 postvaccination
Population: Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of antibody response, developed suspected varicella or herpes zoster rashes before blood sampling, or reported an exposure to varicella or herpes zoster.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ZOSTAVAX™ (AMP) | Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers | 2.3 Ratio |
| ZOSTAVAX™ | Geometric Mean Fold Rise (GMFR) in VZV Antibody Titers | 2.2 Ratio |
Comparison: The hypothesis tested was that ZOSTAVAX™ (AMP) induces an acceptable GMFR in VZV antibody titer from prevaccination to 6 weeks postvaccinationp-value: <0.001t-test, 1 sided
Primary
Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody
VZV antibody titers were determined by glycoprotein enzyme-linked immunosorbent assay (gpELISA)
Time frame: Day 1 and Week 6 postvaccination
Population: Analysis included all vaccinated participants except those who had protocol deviations that interfered with the assessment of antibody response, developed suspected varicella or herpes zoster rashes before blood sampling, or reported an exposure to varicella or herpes zoster
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ZOSTAVAX™ (AMP) | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody | Day 1 postvaccination; n = 330, 166 | 235.7 Units/mL |
| ZOSTAVAX™ (AMP) | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody | Week 6 postvaccination; n = 320, 164 | 532.6 Units/mL |
| ZOSTAVAX™ | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody | Day 1 postvaccination; n = 330, 166 | 208.2 Units/mL |
| ZOSTAVAX™ | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibody | Week 6 postvaccination; n = 320, 164 | 457.1 Units/mL |
Comparison: The hypothesis tested is that the GMT at Week 6 postvaccination with ZOSTAVAX™ (AMP) vaccine is non-inferior to that with the current process vaccinep-value: <0.00195% CI: [0.98, 1.2]Longitudinal regression model
Secondary
Number of Participants With One or More Adverse Experiences (AEs)
An 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.
Time frame: Day 1 to Day 42 postvaccination
Population: Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOSTAVAX™ (AMP) | Number of Participants With One or More Adverse Experiences (AEs) | 205 Participants |
| ZOSTAVAX™ | Number of Participants With One or More Adverse Experiences (AEs) | 99 Participants |
Secondary
Number of Participants With One or More Serious Adverse Experience Day 1 to 182 Postvaccination
An SAE 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: Day 1 to Day 182 postvaccination
Population: Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOSTAVAX™ (AMP) | Number of Participants With One or More Serious Adverse Experience Day 1 to 182 Postvaccination | 4 Participants |
| ZOSTAVAX™ | Number of Participants With One or More Serious Adverse Experience Day 1 to 182 Postvaccination | 8 Participants |
Secondary
Number of Participants With One or More Serious Adverse Experience (SAE) Day 1 to 42 Postvaccination
An SAE 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: Day 1 to Day 42 postvaccination
Population: Analysis included all vaccinated participants with safety follow-up data. One participant in the AMP vaccine group was vaccinated but lost to follow-up without safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOSTAVAX™ (AMP) | Number of Participants With One or More Serious Adverse Experience (SAE) Day 1 to 42 Postvaccination | 1 Participants |
| ZOSTAVAX™ | Number of Participants With One or More Serious Adverse Experience (SAE) Day 1 to 42 Postvaccination | 2 Participants |