Trial Outcomes & Findings for ZOSTAVAX™ Administered Concomitantly With PNEUMOVAX™ 23 (V211-012)(COMPLETED) (NCT NCT00535730)
NCT ID: NCT00535730
Last Updated: 2017-04-12
Results Overview
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
COMPLETED
PHASE3
473 participants
4 weeks postvaccination
2017-04-12
Participant Flow
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.
Participant milestones
| Measure |
Nonconcomitant Group
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Overall Study
STARTED
|
236
|
237
|
|
Overall Study
COMPLETED
|
234
|
230
|
|
Overall Study
NOT COMPLETED
|
2
|
7
|
Reasons for withdrawal
| Measure |
Nonconcomitant Group
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
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
ZOSTAVAX™ Administered Concomitantly With PNEUMOVAX™ 23 (V211-012)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Nonconcomitant Group
n=236 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=235 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
Total
n=471 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.0 years
STANDARD_DEVIATION 5.6 • n=99 Participants
|
66.3 years
STANDARD_DEVIATION 5.6 • n=107 Participants
|
66.2 years
STANDARD_DEVIATION 5.6 • n=206 Participants
|
|
Sex: Female, Male
Female
|
135 Participants
n=99 Participants
|
138 Participants
n=107 Participants
|
273 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=99 Participants
|
97 Participants
n=107 Participants
|
198 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
235 participants
n=99 Participants
|
233 participants
n=107 Participants
|
468 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 4 weeks postvaccinationPopulation: 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.
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
Outcome measures
| Measure |
Nonconcomitant Group
n=225 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=217 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Antibody Responses at 4 Weeks Postvaccination
|
448.5 gpELISA units*/mL
Interval 400.3 to 502.4
|
371.6 gpELISA units*/mL
Interval 328.7 to 420.0
|
PRIMARY outcome
Timeframe: Four weeks postvaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=217 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
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
Interval 1.7 to 2.1
|
—
|
PRIMARY outcome
Timeframe: Four weeks postvaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=228 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=219 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 3 Antibody Response at 4 Weeks Postvaccination.
|
1.2 micrograms/mL
Interval 1.1 to 1.4
|
1.1 micrograms/mL
Interval 1.0 to 1.2
|
PRIMARY outcome
Timeframe: Four weeks postvaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=228 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=219 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 14 Antibody Response at 4 Weeks Postvaccination.
|
26.5 micrograms/mL
Interval 22.9 to 30.8
|
25.7 micrograms/mL
Interval 21.8 to 30.3
|
PRIMARY outcome
Timeframe: Four weeks postvaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=228 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=219 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 19A Antibody Response at 4 Weeks Postvaccination.
|
10.5 micrograms/mL
Interval 8.7 to 12.6
|
10.5 micrograms/mL
Interval 8.7 to 12.7
|
PRIMARY outcome
Timeframe: Four weeks postvaccinationPopulation: 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.
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=228 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=219 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Geometric Mean Titer (GMT) of the Pneumococcal Polysaccharide (PnPs) Serotype 22F Antibody Response at 4 Weeks Postvaccination.
|
2.8 micrograms/mL
Interval 2.3 to 3.3
|
2.5 micrograms/mL
Interval 2.1 to 3.0
|
SECONDARY outcome
Timeframe: Eight weeks postvaccinationPopulation: All subjects who received at least one vaccination
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.
Outcome measures
| Measure |
Nonconcomitant Group
n=236 Participants
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
n=235 Participants
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
Varicella-like Rash
|
3 Participants
|
2 Participants
|
|
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
Injection site AEs
|
141 Participants
|
136 Participants
|
|
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
Systemic AEs
|
74 Participants
|
70 Participants
|
|
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
Serious AEs
|
4 Participants
|
2 Participants
|
|
Safety and Tolerability of Both Vaccines When Administered Concomitantly.
Zoster-like Rash
|
1 Participants
|
1 Participants
|
Adverse Events
Nonconcomitant Group
Concomitant Group
Serious adverse events
| Measure |
Nonconcomitant Group
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/236
|
0.43%
1/235
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/236
|
0.43%
1/235
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.42%
1/236
|
0.00%
0/235
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's Lymphoma
|
0.42%
1/236
|
0.00%
0/235
|
|
Vascular disorders
Haematoma
|
0.42%
1/236
|
0.00%
0/235
|
|
Infections and infestations
Diverticulitis
|
0.42%
1/236
|
0.00%
0/235
|
|
Nervous system disorders
Global amnesia
|
0.42%
1/236
|
0.00%
0/235
|
Other adverse events
| Measure |
Nonconcomitant Group
Subjects were administered PNEUMOVAX™ 23 intramuscularly on Day 1 followed by ZOSTAVAX™ subcutaneously on Week 4
|
Concomitant Group
Subjects were administered ZOSTAVAX™ subcutaneously concomitantly with PNEUMOVAX™ 23 intramuscularly at separate injection sites at Day 1
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
1.3%
3/236
|
0.85%
2/235
|
|
Gastrointestinal disorders
Stomach discomfort
|
0.00%
0/236
|
1.3%
3/235
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
3/236
|
0.00%
0/235
|
|
General disorders
Fatigue
|
1.3%
3/236
|
0.43%
1/235
|
|
General disorders
Malaise
|
0.00%
0/236
|
1.3%
3/235
|
|
General disorders
Pyrexia
|
0.42%
1/236
|
2.1%
5/235
|
|
Infections and infestations
Nasopharyngitis
|
2.1%
5/236
|
3.8%
9/235
|
|
Infections and infestations
Upper respiratory tract infection
|
0.42%
1/236
|
2.1%
5/235
|
|
Infections and infestations
Urinary tract infection
|
1.7%
4/236
|
1.3%
3/235
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.3%
3/236
|
0.43%
1/235
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.1%
5/236
|
1.3%
3/235
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.3%
3/236
|
0.43%
1/235
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.7%
4/236
|
1.7%
4/235
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.7%
4/236
|
0.85%
2/235
|
|
Nervous system disorders
Headache
|
1.7%
4/236
|
5.5%
13/235
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/236
|
1.3%
3/235
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
1.7%
4/236
|
2.1%
5/235
|
|
Skin and subcutaneous tissue disorders
Erythema
|
1.3%
3/236
|
1.3%
3/235
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.3%
3/236
|
0.85%
2/235
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.5%
6/236
|
0.43%
1/235
|
|
Skin and subcutaneous tissue disorders
Rash Vesicular
|
1.7%
4/236
|
1.3%
3/235
|
|
General disorders
Erythema (ZOSTAVAX™ injection site)
|
29.7%
70/236
|
30.6%
72/235
|
|
General disorders
Erythema (PNEUMOVAX™ 23 injection site)
|
12.7%
30/236
|
19.6%
46/235
|
|
General disorders
Erythema (Placebo injection site)
|
3.0%
7/236
|
0.43%
1/235
|
|
General disorders
Induration (ZOSTAVAX™ injection site)
|
1.3%
3/236
|
0.85%
2/235
|
|
General disorders
Pain (ZOSTAVAX™ injection site)
|
28.8%
68/236
|
31.5%
74/235
|
|
General disorders
Pain (PNEUMOVAX™ 23 injection site)
|
34.7%
82/236
|
40.4%
95/235
|
|
General disorders
Pain (Placebo injection site)
|
8.9%
21/236
|
3.4%
8/235
|
|
General disorders
Pruritus (ZOSTAVAX™ injection site)
|
3.4%
8/236
|
4.7%
11/235
|
|
General disorders
Swelling (ZOSTAVAX™ injection site)
|
26.7%
63/236
|
28.5%
67/235
|
|
General disorders
Swelling (PNEUMOVAX™ 23 injection site)
|
12.7%
30/236
|
20.9%
49/235
|
|
General disorders
Swelling (Placebo injection site)
|
2.1%
5/236
|
1.3%
3/235
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER