Herpes Zoster
Conditions
Brief summary
The purpose of the study was to assess the safety, tolerability, and immunogenicity of ZOSTAVAX™ in patients receiving chronic/maintenance corticosteroids.
Interventions
BIOLOGICALZoster Vaccine, Live
A single dose of 0.65 ml Zoster Vaccine, Live, injected subcutaneously on Day 1
BIOLOGICALComparator: Placebo
A single dose of 0.65 ml Placebo to ZOSTAVAX™ injected 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
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Varicella-history positive, herpes zoster (HZ)-history negative patients * 60 years of age and older receiving chronic/maintenance systemic corticosteroid therapy at a daily dose of 5 to 20 mg of prednisone or equivalent for at least the 2 weeks immediately prior to enrollment and expected to continue to receive a daily dose of 5 to 20 mg of prednisone or equivalent for the 6-week primary safety follow-up period (dose may vary within this range during the 6-week postvaccination period) * All females enrolling must be postmenopausal
Exclusion criteria
* Patients with a history of hypersensitivity reaction to gelatin or neomycin * Prior receipt of varicella or zoster vaccine; prior history of herpes zoster * Immune globulin and/or blood products given within 5 months prior to or expected within the 6-week postvaccination period * Receipt of any live virus vaccinations within 1 month or receipt of any inactivated vaccinations within 7 days prior to enrollment * Known immune deficiency that is caused by a medical condition * Any use in the 8 weeks prior to vaccination or for 6 weeks after vaccination other medications which may suppress the immune system including methotrexate, corticosteroids at a daily dose greater than 20 mg of prednisone or equivalent, agents used to treat cancer, or medications which alter the level of the immune response used to treat arthritis or other illnesses * Concomitant use of antiviral therapy * A history of alcohol abuse or recreational drug use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAE) | Up to 182 days postvaccination | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibodies at 42 Days Postvaccination | 42 days postvaccination | The Geometric Mean Titer (GMT) of VZV antibodies in participants' serum samples was assessed by a glycoprotein enzyme-linked immunosorbent assay (gpELISA). |
| Geometric Mean Fold Rise (GMFR) of the VZV Antibody Response From Day 1 to Day 42 Postvaccination. | 42 days postvaccination | The geometric mean fold rise (GMFR) of the VZV antibodies from Day 1 to Week 6 postvaccination. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ZOSTAVAX™ Participants administered ZOSTAVAX™ on Day 1. | 207 |
| Placebo Participants administered Placebo on Day 1. | 102 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | ZOSTAVAX™ | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.8 years STANDARD_DEVIATION 6.9 | 69.9 years STANDARD_DEVIATION 7.2 | 69.8 years STANDARD_DEVIATION 7 |
| Daily Corticosteroid Dose Stratum >10 to 20 mg of prednisone or equivalent | 25 Participants | 14 Participants | 39 Participants |
| Daily Corticosteroid Dose Stratum 5 to 10 mg of prednisone or equivalent | 182 Participants | 88 Participants | 270 Participants |
| Sex: Female, Male Female | 140 Participants | 80 Participants | 220 Participants |
| Sex: Female, Male Male | 67 Participants | 22 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 204 | 10 / 99 |
| serious Total, serious adverse events | 21 / 204 | 11 / 99 |
Outcome results
Primary
Number of Participants With Serious Adverse Events (SAE)
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: Up to 182 days postvaccination
Population: All participants who were vaccinated and had any safety~follow-up were included in the safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZOSTAVAX™ | Number of Participants With Serious Adverse Events (SAE) | 21 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAE) | 11 Participants |
Secondary
Geometric Mean Fold Rise (GMFR) of the VZV Antibody Response From Day 1 to Day 42 Postvaccination.
The geometric mean fold rise (GMFR) of the VZV antibodies from Day 1 to Week 6 postvaccination.
Time frame: 42 days postvaccination
Population: Per-protocol population: All vaccinated participants who had serology results and who had no protocol deviations that would interfere with the evaluation of VZV-specific gpELISA antibody response.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ZOSTAVAX™ | Geometric Mean Fold Rise (GMFR) of the VZV Antibody Response From Day 1 to Day 42 Postvaccination. | 2.3 Ratio |
| Placebo | Geometric Mean Fold Rise (GMFR) of the VZV Antibody Response From Day 1 to Day 42 Postvaccination. | 1.1 Ratio |
Secondary
Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibodies at 42 Days Postvaccination
The Geometric Mean Titer (GMT) of VZV antibodies in participants' serum samples was assessed by a glycoprotein enzyme-linked immunosorbent assay (gpELISA).
Time frame: 42 days postvaccination
Population: Per-protocol population: All vaccinated participants who had serology results and who had no protocol deviations that would interfere with the evaluation of VZV-specific gpELISA antibody response.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ZOSTAVAX™ | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibodies at 42 Days Postvaccination | 531.1 gpELISA units/mL |
| Placebo | Geometric Mean Titer (GMT) of Varicella-Zoster Virus (VZV) Antibodies at 42 Days Postvaccination | 224.3 gpELISA units/mL |