Trial Outcomes & Findings for Immunogenicity and Safety of a 1-dose Regimen of a Zoster Vaccine Versus Different 2-dose Regimens in Participants ≥ 70 Years of Age. (V211-043) (NCT NCT00561080)

Results Overview

Blood samples taken at 4 weeks post each vaccination to determine the geometric mean titer (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

759 participants

Primary outcome timeframe

4 weeks post-dose 1 (Month 1 for all groups) and 4 weeks post-dose 2 (Month 2 for Group 2 and Month 4 for Group 3)

Results posted on

2019-01-11

Participant Flow

A total of 779 participants were screened. Twenty participants were not randomized.

Participant milestones

Participant milestones
Measure	Group 1: Single Dose of Zostavax Single injection of the 0.65 mL of Zostavax administered on Day 0	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 0.65 mL of Zostavax administered on Day 0 and Month 3
Vaccination Period (up to Month 4) STARTED	253	255	251
Vaccination Period (up to Month 4) Received at Least 1 Vaccination	253	254	250
Vaccination Period (up to Month 4) COMPLETED	250	229	225
Vaccination Period (up to Month 4) NOT COMPLETED	3	26	26
12-month Post Last Dose Follow-up STARTED	250	229	225
12-month Post Last Dose Follow-up COMPLETED	243	220	215
12-month Post Last Dose Follow-up NOT COMPLETED	7	9	10
24-month Post Last Dose Follow-up STARTED	0	0	0
24-month Post Last Dose Follow-up COMPLETED	0	0	0
24-month Post Last Dose Follow-up NOT COMPLETED	0	0	0
36 Month Post Last Dose Follow-up STARTED	0	0	0
36 Month Post Last Dose Follow-up COMPLETED	0	0	0
36 Month Post Last Dose Follow-up NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Single Dose of Zostavax Single injection of the 0.65 mL of Zostavax administered on Day 0	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 0.65 mL of Zostavax administered on Day 0 and Month 3
Vaccination Period (up to Month 4) Adverse Event	0	4	6
Vaccination Period (up to Month 4) Definitive Contra-indication	0	2	3
Vaccination Period (up to Month 4) Protocol Violation	0	1	3
Vaccination Period (up to Month 4) Withdrawal by Subject	3	16	13
Vaccination Period (up to Month 4) Lost to Follow-up	0	1	0
Vaccination Period (up to Month 4) Other	0	2	1
12-month Post Last Dose Follow-up Adverse Event	3	3	1
12-month Post Last Dose Follow-up Protocol Violation	0	0	4
12-month Post Last Dose Follow-up Withdrawal by Subject	2	6	5
12-month Post Last Dose Follow-up Lost to Follow-up	2	0	0

Baseline Characteristics

Baseline age missing for 1 participant in Group 2 and 1 participant in Group 3.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Single Dose of Zostavax n=253 Participants Single injection of the 0.65 mL of Zostavax administered on Day 0	Group 2: Zostavax - Day 0 and Month 1 n=255 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=251 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Total n=759 Participants Total of all reporting groups
Age, Continuous	76.2 years STANDARD_DEVIATION 5.5 • n=253 Participants • Baseline age missing for 1 participant in Group 2 and 1 participant in Group 3.	76.0 years STANDARD_DEVIATION 5.4 • n=254 Participants • Baseline age missing for 1 participant in Group 2 and 1 participant in Group 3.	76.1 years STANDARD_DEVIATION 5.3 • n=250 Participants • Baseline age missing for 1 participant in Group 2 and 1 participant in Group 3.	76.1 years STANDARD_DEVIATION 5.4 • n=757 Participants • Baseline age missing for 1 participant in Group 2 and 1 participant in Group 3.
Sex: Female, Male Female	148 Participants n=253 Participants	138 Participants n=255 Participants	135 Participants n=251 Participants	421 Participants n=759 Participants
Sex: Female, Male Male	105 Participants n=253 Participants	117 Participants n=255 Participants	116 Participants n=251 Participants	338 Participants n=759 Participants

PRIMARY outcome

Timeframe: 4 weeks post-dose 1 (Month 1 for all groups) and 4 weeks post-dose 2 (Month 2 for Group 2 and Month 4 for Group 3)

Population: All randomized participants in Groups 2 and 3 who received at least 1 dose of the study vaccine, had post-vaccination immunogenicity evaluation and excluded those with protocol violation which may have interfered with the immunogenicity evaluation or participants with herpes zoster (HZ) onset before the time point for analysis.

Blood samples taken at 4 weeks post each vaccination to determine the geometric mean titer (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA).

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=203 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=198 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 0.65 mL of Zostavax administered on Day 0 and Month 3
Geometric Mean Titer (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks After Each Vaccination: Groups 2 and 3 Post Dose 1	498.8 gpELISA units/mL Interval 438.7 to 567.1	523.3 gpELISA units/mL Interval 459.0 to 596.7	—
Geometric Mean Titer (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks After Each Vaccination: Groups 2 and 3 Post Dose 2	555.3 gpELISA units/mL Interval 496.6 to 620.9	410.5 gpELISA units/mL Interval 363.1 to 464.2	—

SECONDARY outcome

Timeframe: 4 weeks post-dose (Month 1)

Population: All randomized participants in Group 1 who received study vaccine, had post-vaccination immunogenicity evaluation and excluded those with protocol violation which may have interfered with the immunogenicity evaluation or participants with herpes zoster (HZ) onset before the time point for analysis.

Blood sample taken at 4 weeks post vaccination to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=243 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 0.65 mL of Zostavax administered on Day 0 and Month 3
Geometric Mean Titer (GMT) of VZV Antibodies 4 Weeks After Vaccination: Group 1 GMT Pre-Dose	233.7 gpELISA units/mL Interval 207.1 to 263.7	—	—
Geometric Mean Titer (GMT) of VZV Antibodies 4 Weeks After Vaccination: Group 1 GMT Post Dose	550.0 gpELISA units/mL Interval 489.2 to 618.4	—	—

SECONDARY outcome

Timeframe: Predose and 4 weeks post-dose 1 (Month 1 for all groups) and 4 weeks post-dose 2 (Month 2 for Group 2 and Month 4 for Group 3)

Population: All randomized participants in who received at least 1 dose of the study vaccine, had pre-dose 1 evaluation and had post-vaccination immunogenicity evaluation. Excluded those with protocol violation which may have interfered with the immunogenicity evaluation or participants with herpes zoster (HZ) onset before the time point for analysis.

Blood sample taken at predose (Day 0) and 4 weeks post each vaccination to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA. The GMFR was calculated following each vaccination as GMT Post-dose/GMT Pre-vaccination

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=242 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=203 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=198 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titres From Pre-vaccination to 4 Weeks Post-dose 1 in Groups 1, 2 and 3 and 4 Weeks Post-dose 2 in Groups 2 and 3 GMFR Post Dose 1	2.35 gpELISA units/mL Interval 2.11 to 2.62	2.37 gpELISA units/mL Interval 2.11 to 2.66	2.29 gpELISA units/mL Interval 2.05 to 2.57
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titres From Pre-vaccination to 4 Weeks Post-dose 1 in Groups 1, 2 and 3 and 4 Weeks Post-dose 2 in Groups 2 and 3 GMFR Post Dose 2	NA gpELISA units/mL Group 1 did not have 2nd vaccination	2.64 gpELISA units/mL Interval 2.37 to 2.95	1.80 gpELISA units/mL Interval 1.63 to 1.98

SECONDARY outcome

Timeframe: 1 year post final dose for Groups 1, 2, and 3 (Group 1: Month 12; Group 2: 13 Month 13; and Group 3: Month 15)

Population: All randomized participants in who received at least 1 dose of the study vaccine, had 12-month post-vaccination immunogenicity evaluation and excluded those with protocol violation which may have interfered with the immunogenicity evaluation or participants with herpes zoster (HZ) onset before the time point for analysis.

Blood sample taken at 1 year post last vaccination to determine the geometric mean titer (GMT) of varicella antibodies via gpELISA.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=223 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=189 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=204 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Geometric Mean Titre of VZV Antibodies 12 Months Post-last Dose	246.8 gpELISA units/mL Interval 230.9 to 263.9	261.1 gpELISA units/mL Interval 242.8 to 280.7	266.6 gpELISA units/mL Interval 248.6 to 285.8

SECONDARY outcome

Timeframe: predose 1 and 1 year post-last dose (Group 1: Month 12; Group 2: 13 Month 13; and Group 3: Month 15)

Population: All randomized participants who received at least 1 dose of the study vaccine, had 12-month post-vaccination immunogenicity evaluation and excluded those with protocol violation which may have interfered with the immunogenicity evaluation or participants with herpes zoster (HZ) onset before the time point for analysis.

Blood sample taken at predose and 1 year post last vaccination to determine the GMFR of varicella antibodies via gpELISA. Geometric mean fold rise was calculated for each arm as GMT 12-month post last dose divided by pre-vaccination GMT.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=223 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=189 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=204 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Geometric Mean Fold Rise (GMFR) in VZV Antibody Titres From Pre-Vaccination To 12 Months Post-dose 1 in Group 1 And From Pre-Vaccination To 12 Months Post-dose 2 in Groups 2 and 3	1.06 gpELISA units/mL Interval 0.99 to 1.14	1.16 gpELISA units/mL Interval 1.06 to 1.26	1.17 gpELISA units/mL Interval 1.07 to 1.27

SECONDARY outcome

Timeframe: 24 and 36 months post-last dose

Population: Study stopped after 12 months. As per protocol, the study was stopped after the 12-month follow-up since there was no statistical evidence or clinical trend for superiority of any of the 2-dose regimens compared with the 1-dose regimen. 24 and 36 month data not obtained.

Blood sample taken at 36 months post last-vaccination to determine the geometric mean titer (GMT) of varicella antibodies via gpELISA.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose 1 and 24 and 36 months post-last dose

Population: Study stopped after 12 months. As per protocol, the study was stopped after the 12-month follow-up since there was no statistical evidence or clinical trend for superiority of any of the 2-dose regimens compared with the 1-dose regimen. 24 and 36 month data not obtained.

Blood samples were to be taken at predose and 24 months post- last vaccination in Groups 1 , 2, and 3 to determine the GMFR of varicella antibodies via gpELISA. Geometric mean fold rise was to be calculated for each arm as GMT 24-month post last dose divided by pre-vaccination GMT.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 4 days after 1st vaccination

Population: All randomized participants in Groups 1, 2 and 3 who received the 1st dose of study drug and had follow-up safety data. .

Participants entered data into daily dairy card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Solicited Injection Site Reaction : Post-dose 1	47.2 Percentage of Participants	46.0 Percentage of Participants	42.2 Percentage of Participants

SECONDARY outcome

Timeframe: up to 4 days after 2nd vaccination

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of study drug and had follow-up safety data.

Participants entered data into daily dairy card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Solicited Injection Site Reaction: Post-dose 2	—	42.2 Percentage of Participants	42.1 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 1st of study drug

Population: All randomized participants in Groups 1, 2, and 3 who received at least 1 dose of study drug and had follow-up safety data. .

The percentage of participants who reported an injection site reaction that was not specifically prompted by the diary card within 28 day of 1st vaccination was recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 1	5.6 Percentage of Participants	4.8 Percentage of Participants	0.8 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days post-dose 2

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of study drug and had follow-up safety data. .

The percentage of participants that reported an injection site reaction that was not specifically prompted by the diary card within 28 days post-dose 2 was recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 2	—	1.3 Percentage of Participants	3.2 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days post-dose 1

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of the study drug and who have safety follow-up data for post-dose 1.

Percentage of participants who reported herpes zoster or zoster-like rash following the 1st dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-dose 1	0.8 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days post-dose 2

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of the study drug and who have safety follow-up data for post-dose 2.

Percentage of participants who reported herpes zoster or zoster-like rash following the 2nd dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-Dose 2	—	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days post-dose 1

Population: All randomized participants in Groups 1, 2 and 3 who received 1st dose of the study drug and who have safety follow-up data for post-dose 1.

Percentage of participants that reported varicella or varicella-like rash following the 1st dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 1	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days post-dose 2

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of the study drug and who have safety follow-up data for post-dose 2.

Percentage of participants that reported varicella or varicella-like rash following the 2nd dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 2	—	0.4 Percentage of Participants	0.5 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 1st vaccination

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of study drug and had follow-up safety data. .

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) were summarized

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 1	25.8 Percentage of Participants	32.7 Percentage of Participants	25.7 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 2nd vaccination

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of study drug and had follow-up safety data.

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) were summarized,

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 2	—	20.7 Percentage of Participants	15.4 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 1st vaccination

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of study drug and had follow-up safety data. .

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) and were reported as at least possibly related to the vaccine were summarized

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 1	6.7 Percentage of Participants	4.0 Percentage of Participants	8.4 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 2nd vaccination

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of study drug and had follow-up safety data.

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Adverse events that were considered systemic (not localized) and were reported as at least possibly related to the vaccine were summarized,

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 2	—	3.4 Percentage of Participants	2.7 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 1st vaccination

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of study drug and had follow-up safety data.

A serious adverse event (SAE) is 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. The percentage of participants who reported an SAE within 28 days of 1st dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 1	0.4 Percentage of Participants	2.8 Percentage of Participants	0.4 Percentage of Participants

SECONDARY outcome

Timeframe: up to 28 days after 2nd vaccination

Population: All randomized participants in Groups 2 and 3 who received 2nd dose of study drug and had follow-up safety data.

A serious adverse event (SAE) is 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. The percentage of participants who reported an SAE within 28 days of 1st dose of vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=232 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=221 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 2	—	0.9 Percentage of Participants	0.9 Percentage of Participants

SECONDARY outcome

Timeframe: up to end of study (approximately 15 months)

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of study drug and had follow-up safety data.

A serious adverse event (SAE) is 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. The percentage of participants who reported an SAE during the entire study period that was considered at least possibly -related to the vaccine were recorded.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Reported a Vaccine-related Serious Adverse Event	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: up to end of study (approximately 15 months)

Population: All randomized participants in Groups 1, 2, and 3 who received 1st dose of study drug and had follow-up safety data.

The number of participants who died for any reason during the study was summarized.

Outcome measures

Outcome measures
Measure	Group 2: Zostavax - Day 0 and Month 1 n=252 Participants 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=248 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3	Group 3: Zostavax - Day 0 and Month 3 n=249 Participants 0.65 mL of Zostavax administered on Day 0 and Month 3
Percentage of Participants Who Died During the Study	1.6 Percentage of Participants	2.0 Percentage of Participants	1.2 Percentage of Participants

Adverse Events

Group 1: Single Dose of Zostavax

Serious events: 4 serious events

Other events: 122 other events

Deaths: 0 deaths

Group 2: Zostavax - Day 0 and Month 1

Serious events: 11 serious events

Other events: 144 other events

Deaths: 0 deaths

Group 3: Zostavax - Day 0 and Month 3

Serious events: 4 serious events

Other events: 132 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Group 1: Single Dose of Zostavax n=253 participants at risk Single injection of the 0.65 mL of Zostavax administered on Day 0	Group 2: Zostavax - Day 0 and Month 1 n=255 participants at risk 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=251 participants at risk 0.65 mL of Zostavax administered on Day 0 and Month 3
General disorders Injection site erythema	42.3% 107/253 • Number of events 107 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	49.0% 125/255 • Number of events 185 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	48.6% 122/251 • Number of events 181 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
General disorders Injection site pain	22.5% 57/253 • Number of events 60 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	29.4% 75/255 • Number of events 98 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	29.5% 74/251 • Number of events 101 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
General disorders Injection site swelling	27.3% 69/253 • Number of events 69 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	28.6% 73/255 • Number of events 106 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	26.7% 67/251 • Number of events 92 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Nervous system disorders Headache	5.1% 13/253 • Number of events 16 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	5.5% 14/255 • Number of events 18 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	4.0% 10/251 • Number of events 16 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators must first obtain written consent from Sanofi Pasteur MSD. If consent is given, all abstracts manuscripts, texts, or presentation, etc... shall be sent to Sanofi Pasteur MSD for review and approval prior to their publication or presentation. Sanofi Pasteur MSD shall have sixty days to review these documents and may refuse to give its consent in part or whole for confidential reasons (including but not limited to intellectual property rights, whether patentable or not).
Publication restrictions are in place

Restriction type: OTHER

Measure	Group 1: Single Dose of Zostavax n=253 participants at risk Single injection of the 0.65 mL of Zostavax administered on Day 0	Group 2: Zostavax - Day 0 and Month 1 n=255 participants at risk 0.65 mL of Zostavax administered on Day 0 and Month 1	Group 3: Zostavax - Day 0 and Month 3 n=251 participants at risk 0.65 mL of Zostavax administered on Day 0 and Month 3
Cardiac disorders Angina pectoris	0.40% 1/253 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Cardiac disorders Atrial fibrillation	0.40% 1/253 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Cardiac disorders Cardiac failure	0.40% 1/253 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Cardiac disorders Cardiogenic shock	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Cardiac disorders Coronary artery disease	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.40% 1/251 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Cardiac disorders Myocardial infarction	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.78% 2/255 • Number of events 2 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Gastrointestinal disorders Ileus	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Infections and infestations Bronchitis	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Infections and infestations Diverticulitis	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.40% 1/251 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Infections and infestations Erysipelas	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Infections and infestations Gastroenteritis	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.40% 1/251 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.40% 1/251 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Metabolism and nutrition disorders Dehydration	0.40% 1/253 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/255 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.40% 1/251 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Psychiatric disorders Mental disorder due to a general medical condition	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Vascular disorders Hypertension	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.
Vascular disorders Peripheral embolism	0.00% 0/253 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.39% 1/255 • Number of events 1 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.	0.00% 0/251 • up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total) Analysis population is all enrolled participants.