Trial Outcomes & Findings for Study to Evaluate Immunogenicity, Safety, and Tolerability of ZOSTAVAX™ Vaccine (Zoster Vaccine Live, V211) Administered Concomitantly Versus Nonconcomitantly With Quadrivalent Influenza Virus Vaccine (Inactivated) in Participants ≥50 Years of Age (V211-062) (NCT NCT02519855)
NCT ID: NCT02519855
Last Updated: 2018-10-30
Results Overview
Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group.
COMPLETED
PHASE3
882 participants
Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group)
2018-10-30
Participant Flow
A total of 901 participants were screened and 882 were randomized to one of two vaccination groups.
Participant milestones
| Measure |
Concomitant Vaccination
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Overall Study
STARTED
|
441
|
441
|
|
Overall Study
Vaccinated on Day 1
|
440
|
441
|
|
Overall Study
Vaccinated at Week 4
|
432
|
424
|
|
Overall Study
COMPLETED
|
438
|
437
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Concomitant Vaccination
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
3
|
3
|
Baseline Characteristics
Study to Evaluate Immunogenicity, Safety, and Tolerability of ZOSTAVAX™ Vaccine (Zoster Vaccine Live, V211) Administered Concomitantly Versus Nonconcomitantly With Quadrivalent Influenza Virus Vaccine (Inactivated) in Participants ≥50 Years of Age (V211-062)
Baseline characteristics by cohort
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=442 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
Total
n=882 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.8 Years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
61.3 Years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
61.0 Years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
266 Participants
n=5 Participants
|
262 Participants
n=7 Participants
|
528 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
174 Participants
n=5 Participants
|
180 Participants
n=7 Participants
|
354 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group.
Outcome measures
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=441 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody
Baseline, n=427, 409
|
206.0 gpELISA units/mL
Interval 185.6 to 228.6
|
230.5 gpELISA units/mL
Interval 208.4 to 255.0
|
|
Geometric Mean Titer (GMT) of Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody
Week 4, n=409, 392
|
395.6 gpELISA units/mL
Interval 363.7 to 430.4
|
482.0 gpELISA units/mL
Interval 446.4 to 520.4
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group.
Outcome measures
| Measure |
Concomitant Vaccination
n=403 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=387 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers
|
1.9 Ratio of titers (Week 4 / Baseline)
Interval 1.8 to 2.1
|
2.1 Ratio of titers (Week 4 / Baseline)
Interval 1.9 to 2.2
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after Influenza vaccination (Week 4)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Antibodies to H1N1-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Outcome measures
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=441 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Titers of H1N1-specific Influenza Virus Antibody
Baseline, n=426, 427
|
51.9 Titer
Interval 45.4 to 59.3
|
50.1 Titer
Interval 44.3 to 56.7
|
|
Geometric Mean Titers of H1N1-specific Influenza Virus Antibody
Week 4, n=409, 405
|
207.3 Titer
Interval 185.6 to 231.7
|
200.5 Titer
Interval 180.3 to 222.9
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after Influenza vaccination (Week 4)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Antibodies to H3N2-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Outcome measures
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=441 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Titers of H3N2-specific Influenza Virus Antibody
Baseline, n=426, 427
|
29.5 Titer
Interval 26.2 to 33.3
|
31.1 Titer
Interval 27.5 to 35.1
|
|
Geometric Mean Titers of H3N2-specific Influenza Virus Antibody
Week 4, n=409, 405
|
298.8 Titer
Interval 264.1 to 338.1
|
272.0 Titer
Interval 241.6 to 306.1
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after Influenza vaccination (Week 4)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Antibodies to B-Yamagata-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Outcome measures
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=441 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody
Baseline, n=426, 427
|
14.6 Titer
Interval 13.3 to 16.1
|
12.6 Titer
Interval 11.6 to 13.7
|
|
Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody
Week 4, n=409, 405
|
46.7 Titer
Interval 42.0 to 52.0
|
43.9 Titer
Interval 39.7 to 48.6
|
PRIMARY outcome
Timeframe: Baseline and 4 weeks after Influenza vaccination (Week 4)Population: Participants who met the inclusion criteria, were not protocol violators in a way that could influence the participant's immune response to study vaccine, received the quadrivalent influenza vaccine and ZOSTAVAX™ within the specified day ranges, and had samples for serology obtained within the specified day ranges.
Antibodies to B-Victoria-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin.
Outcome measures
| Measure |
Concomitant Vaccination
n=440 Participants
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=441 Participants
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody
Baseline, n=426, 427
|
11.2 Titer
Interval 10.3 to 12.2
|
10.4 Titer
Interval 9.6 to 11.2
|
|
Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody
Week 4, n=409, 405
|
33.9 Titer
Interval 30.5 to 37.7
|
32.3 Titer
Interval 29.0 to 35.9
|
Adverse Events
Concomitant Vaccination
Nonconcomitant Vaccination
Serious adverse events
| Measure |
Concomitant Vaccination
n=435 participants at risk
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=438 participants at risk
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
General disorders
Chest pain
|
0.23%
1/435 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.00%
0/438 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Hepatobiliary disorders
Biliary colic
|
0.23%
1/435 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.00%
0/438 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.23%
1/435 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.00%
0/438 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ureteric cancer local
|
0.23%
1/435 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.00%
0/438 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/435 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
0.23%
1/438 • Number of events 1 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
Other adverse events
| Measure |
Concomitant Vaccination
n=435 participants at risk
ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4
|
Nonconcomitant Vaccination
n=438 participants at risk
Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4
|
|---|---|---|
|
General disorders
Injection site erythema
|
35.2%
153/435 • Number of events 186 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
30.6%
134/438 • Number of events 150 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
General disorders
Injection site pain
|
48.0%
209/435 • Number of events 322 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
48.2%
211/438 • Number of events 335 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
General disorders
Injection site pruritus
|
7.6%
33/435 • Number of events 38 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
7.3%
32/438 • Number of events 33 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
|
General disorders
Injection site swelling
|
23.4%
102/435 • Number of events 125 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
24.9%
109/438 • Number of events 125 • Up to 28 days after any vaccination (up to Week 8)
The population analyzed was all randomized participants who received at least one dose of study vaccination and had follow-up.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
- Publication restrictions are in place
Restriction type: OTHER