Herpes Zoster, Pneumococcal Infection
Conditions
Brief summary
The purpose of this study is to determine whether Zoster Vaccine Live and Pneumococcal Vaccine, polyvalent are as well tolerated and immunogenic when the vaccines are given together (in different body sites), as when they are given alone, in adults 60 years of age and older.
Interventions
BIOLOGICALZoster Vaccine, Live, (Oka-Merck), ZOSTAVAX™
0.65 mL injection Zoster Vaccine, Live, (Oka-Merck) over 4 week vaccination period
BIOLOGICALComparator: placebo (concomitant-vaccine matched)
Pneumococcal Vaccine, Polyvalent (23-valent) 0.5 mL Placebo injection over 4 week vaccination period.
BIOLOGICALPneumococcal Vaccine, Polyvalent (23-valent), PNEUMOVAX™ 23
Pneumococcal Vaccine, Polyvalent (23-valent) 0.5 mL injection over 4 week vaccination period.
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
Yes
Inclusion criteria
* 60 years of age or older * Stable underlying conditions * Postmenopausal if female * Afebrile
Exclusion criteria
* Previously vaccinated with either vaccine * Immune deficiency * History of allergy to components in either vaccine * Concomitant antiviral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 3 Antibody Response at 4 Weeks Postvaccination. | Four weeks postvaccination | GMT of the PnPs serotype 3 antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. |
| Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Antibody Responses at 4 Weeks Postvaccination | 4 weeks postvaccination | GMT of the VZV antibody responses at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. \*gpELISA = glycoprotein enzyme-linked immunosorbent assay |
| Geometric Mean Fold Rise (GMFR) of the Varicella-zoster Virus (VZV) Antibody Responses From Day 1 to 4 Weeks Postvaccination. | Four weeks postvaccination | GMFR of the VZV antibody response from prevaccination to Week 4 postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23. gpELISA = glycoprotein enzyme-linked immunosorbent assay. |
| Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 22F Antibody Response at 4 Weeks Postvaccination. | Four weeks postvaccination | GMT of the PnPs serotype 22F antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. |
| Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 14 Antibody Response at 4 Weeks Postvaccination. | Four weeks postvaccination | GMT of the PnPs serotype 14 antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. |
| Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 19A Antibody Response at 4 Weeks Postvaccination. | Four weeks postvaccination | GMT of the PnPs serotype 19A antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Eight weeks postvaccination | All adverse events were analyzed including serious adverse events; injection-site adverse events; Vaccination Report Card prompted systemic adverse events, including varicella-like rashes or herpes zoster-like rashes; all other systemic adverse events. |
Participant flow
Recruitment details
Phase III First subject enrolled on 18-Jun-2007. Last subject enrolled on 05-Dec-2007. The last subject's last visit was 11-Feb-2008. The study was conducted at 18 study centers throughout Canada, Australia, and Europe.
Participants by arm
| Arm | Count |
|---|---|
| Nonconcomitant Group Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4 | 236 |
| Concomitant Group Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1 | 235 |
| Total | 471 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Nonconcomitant Group | Concomitant Group | Total |
|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 5.6 | 66.3 years STANDARD_DEVIATION 5.6 | 66.2 years STANDARD_DEVIATION 5.6 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 235 participants | 233 participants | 468 participants |
| Sex: Female, Male Female | 135 Participants | 138 Participants | 273 Participants |
| Sex: Female, Male Male | 101 Participants | 97 Participants | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 154 / — | 143 / — |
| serious Total, serious adverse events | 4 / — | 2 / — |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) of the Varicella-zoster Virus (VZV) Antibody Responses From Day 1 to 4 Weeks Postvaccination.
GMFR of the VZV antibody response from prevaccination to Week 4 postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23. gpELISA = glycoprotein enzyme-linked immunosorbent assay.
Time frame: Four weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window; exposure to herpes zoster (HZ) or VZV.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Fold Rise (GMFR) of the Varicella-zoster Virus (VZV) Antibody Responses From Day 1 to 4 Weeks Postvaccination. | 1.9 gpELISA units/mL |
Comparison: The hypothesis was that ZOSTAVAX™ elicits an acceptable VZV antibody response when administered concomitantly with PNEUMOVAX™ 23.p-value: <0.001t-test, 1 sided
Primary
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 14 Antibody Response at 4 Weeks Postvaccination.
GMT of the PnPs serotype 14 antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly.
Time frame: Four weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: prior receipt of a pneumococcal vaccine; receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 14 Antibody Response at 4 Weeks Postvaccination. | 26.5 micrograms/mL |
| Concomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 14 Antibody Response at 4 Weeks Postvaccination. | 25.7 micrograms/mL |
Comparison: The hypothesis was that the GMT of the PnPs antibody responses to serotype 14 at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 will be noninferior to those in subjects who receive ZOSTAVAX™ nonconcomitantly.p-value: <0.001longitudinal regression model
Primary
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 19A Antibody Response at 4 Weeks Postvaccination.
GMT of the PnPs serotype 19A antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly.
Time frame: Four weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: prior receipt of a pneumococcal vaccine; receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 19A Antibody Response at 4 Weeks Postvaccination. | 10.5 micrograms/mL |
| Concomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 19A Antibody Response at 4 Weeks Postvaccination. | 10.5 micrograms/mL |
Comparison: The hypothesis was that the GMT of the PnPs antibody responses to serotype 19A at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 will be noninferior to those in subjects who receive ZOSTAVAX™ nonconcomitantly.p-value: <0.001longitudinal regression model
Primary
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 22F Antibody Response at 4 Weeks Postvaccination.
GMT of the PnPs serotype 22F antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly.
Time frame: Four weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: prior receipt of a pneumococcal vaccine; receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 22F Antibody Response at 4 Weeks Postvaccination. | 2.8 micrograms/mL |
| Concomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 22F Antibody Response at 4 Weeks Postvaccination. | 2.5 micrograms/mL |
Comparison: The hypothesis was that the GMT of the PnPs antibody responses to serotype 22F at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 will be noninferior to those in subjects who receive ZOSTAVAX™ nonconcomitantly.p-value: <0.001longitudinal regression model
Primary
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 3 Antibody Response at 4 Weeks Postvaccination.
GMT of the PnPs serotype 3 antibody response at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly.
Time frame: Four weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: prior receipt of a pneumococcal vaccine; receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 3 Antibody Response at 4 Weeks Postvaccination. | 1.2 micrograms/mL |
| Concomitant Group | Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 3 Antibody Response at 4 Weeks Postvaccination. | 1.1 micrograms/mL |
Comparison: The hypothesis was that the GMT of the PnPs antibody response to serotype 3 at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 will be noninferior to those in subjects who~receive ZOSTAVAX™ nonconcomitantly.p-value: <0.001longitudinal regression model
Primary
Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Antibody Responses at 4 Weeks Postvaccination
GMT of the VZV antibody responses at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 and those who receive ZOSTAVAX™ and PNEUMOVAX™ 23 nonconcomitantly. \*gpELISA = glycoprotein enzyme-linked immunosorbent assay
Time frame: 4 weeks postvaccination
Population: Analysis was per protocol. The following protocol violations resulted in exclusion of subjects from analysis: receipt of prohibited medications; vaccine temperature compromised prior to administration; excluded medical condition; samples collected outside of Statistical Analysis Plan specified time window; exposure to herpes zoster (HZ) or VZV.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nonconcomitant Group | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Antibody Responses at 4 Weeks Postvaccination | 448.5 gpELISA units*/mL |
| Concomitant Group | Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Antibody Responses at 4 Weeks Postvaccination | 371.6 gpELISA units*/mL |
Comparison: The hypothesis was that the GMT of the VZV antibody responses at 4 weeks postvaccination in subjects who receive ZOSTAVAX™ concomitantly with PNEUMOVAX™ 23 will be noninferior to that in subjects who receive ZOSTAVAX™ nonconcomitantlyp-value: 0.244longitudinal regression model
Secondary
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
All adverse events were analyzed including serious adverse events; injection-site adverse events; Vaccination Report Card prompted systemic adverse events, including varicella-like rashes or herpes zoster-like rashes; all other systemic adverse events.
Time frame: Eight weeks postvaccination
Population: All subjects who received at least one vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nonconcomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Systemic AEs | 74 Participants |
| Nonconcomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Varicella-like Rash | 3 Participants |
| Nonconcomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Serious AEs | 4 Participants |
| Nonconcomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Zoster-like Rash | 1 Participants |
| Nonconcomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Injection site AEs | 141 Participants |
| Concomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Zoster-like Rash | 1 Participants |
| Concomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Injection site AEs | 136 Participants |
| Concomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Systemic AEs | 70 Participants |
| Concomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Serious AEs | 2 Participants |
| Concomitant Group | Safety and Tolerability of Both Vaccines When Administered Concomitantly. | Varicella-like Rash | 2 Participants |