NCT00561080

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)

Completed Phase 3 Results posted Last updated 11 January 2019

What this trial tests

Phase 3 trial testing Zostavax in Prevention of : Herpes-Zoster in 759 participants. Completed in 3 June 2009.

Timeline

26 October 2007

Primary endpoint
3 June 2009

3 June 2009

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	759
Start date	26 October 2007
Primary completion	3 June 2009
Estimated completion	3 June 2009

Drugs / interventions tested

• Zostavax

Conditions studied

• Prevention of : Herpes-Zoster — all drugs for Prevention of : Herpes-Zoster →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

70 and older, any sex, with Prevention of : Herpes-Zoster. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Geometric Mean Titer (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks After Each Vaccination: Groups 2 and 3 Primary · 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)

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).

Post Dose 1

Group	Value	95% CI
Group 2: Zostavax - Day 0 and Month 1	498.8	438.7 – 567.1
Group 3: Zostavax - Day 0 and Month 3	523.3	459.0 – 596.7

Post Dose 2

Group	Value	95% CI
Group 2: Zostavax - Day 0 and Month 1	555.3	496.6 – 620.9
Group 3: Zostavax - Day 0 and Month 3	410.5	363.1 – 464.2

Geometric Mean Titer (GMT) of VZV Antibodies 4 Weeks After Vaccination: Group 1 Secondary · 4 weeks post-dose (Month 1)

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

GMT Pre-Dose

Group	Value	95% CI
Group 1: Single Dose of Zostavax	233.7	207.1 – 263.7

GMT Post Dose

Group	Value	95% CI
Group 1: Single Dose of Zostavax	550.0	489.2 – 618.4

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 Secondary · 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)

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

GMFR Post Dose 1

Group	Value	95% CI
Group 1: Single Dose of Zostavax	2.35	2.11 – 2.62
Group 2: Zostavax - Day 0 and Month 1	2.37	2.11 – 2.66
Group 3: Zostavax - Day 0 and Month 3	2.29	2.05 – 2.57

GMFR Post Dose 2

Group	Value	95% CI
Group 1: Single Dose of Zostavax	NA	NA – NA
Group 2: Zostavax - Day 0 and Month 1	2.64	2.37 – 2.95
Group 3: Zostavax - Day 0 and Month 3	1.80	1.63 – 1.98

Geometric Mean Titre of VZV Antibodies 12 Months Post-last Dose Secondary · 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)

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

Group	Value	95% CI
Group 1: Single Dose of Zostavax	246.8	230.9 – 263.9
Group 2: Zostavax - Day 0 and Month 1	261.1	242.8 – 280.7
Group 3: Zostavax - Day 0 and Month 3	266.6	248.6 – 285.8

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

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.

Group	Value	95% CI
Group 1: Single Dose of Zostavax	1.06	0.99 – 1.14
Group 2: Zostavax - Day 0 and Month 1	1.16	1.06 – 1.26
Group 3: Zostavax - Day 0 and Month 3	1.17	1.07 – 1.27

Percentage of Participants Who Reported a Solicited Injection Site Reaction : Post-dose 1 Secondary · up to 4 days after 1st vaccination

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

Group	Value	95% CI
Group 1: Single Dose of Zostavax	47.2
Group 2: Zostavax - Day 0 and Month 1	46.0
Group 3: Zostavax - Day 0 and Month 3	42.2

Percentage of Participants Who Reported a Solicited Injection Site Reaction: Post-dose 2 Secondary · up to 4 days after 2nd vaccination

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

Group	Value	95% CI
Group 2: Zostavax - Day 0 and Month 1	42.2
Group 3: Zostavax - Day 0 and Month 3	42.1

Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 1 Secondary · up to 28 days after 1st of study drug

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.

Group	Value	95% CI
Group 1: Single Dose of Zostavax	5.6
Group 2: Zostavax - Day 0 and Month 1	4.8
Group 3: Zostavax - Day 0 and Month 3	0.8

Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 2 Secondary · up to 28 days post-dose 2

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.

Group	Value	95% CI
Group 2: Zostavax - Day 0 and Month 1	1.3
Group 3: Zostavax - Day 0 and Month 3	3.2

Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-dose 1 Secondary · up to 28 days post-dose 1

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

Group	Value	95% CI
Group 1: Single Dose of Zostavax	0.8
Group 2: Zostavax - Day 0 and Month 1	0.0
Group 3: Zostavax - Day 0 and Month 3	0.0

Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-Dose 2 Secondary · up to 28 days post-dose 2

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

Group	Value	95% CI
Group 2: Zostavax - Day 0 and Month 1	0.0
Group 3: Zostavax - Day 0 and Month 3	0.0

Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 1 Secondary · up to 28 days post-dose 1

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

Group	Value	95% CI
Group 1: Single Dose of Zostavax	0.0
Group 2: Zostavax - Day 0 and Month 1	0.0
Group 3: Zostavax - Day 0 and Month 3	0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 1 year post-last dose (Group 1: 12 months total; Group 2: 13 months total; Group 3: 14 months total). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1: Single Dose of Zostavax

Serious: 4/253 (2%)

Deaths: —

Group 2: Zostavax - Day 0 and Month 1

Serious: 11/255 (4%)

Deaths: —

Group 3: Zostavax - Day 0 and Month 3

Serious: 4/251 (2%)

Deaths: —

Serious adverse events (19 terms)

Reaction	System	Group 1: Single Dose of Zo…	Group 2: Zostavax - Day 0 …	Group 3: Zostavax - Day 0 …
Myocardial infarction	Cardiac disorders	—	—	—
Angina pectoris	Cardiac disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Cardiogenic shock	Cardiac disorders	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—
Ileus	Gastrointestinal disorders	—	—	—
Bronchitis	Infections and infestations	—	—	—
Diverticulitis	Infections and infestations	—	—	—
Erysipelas	Infections and infestations	—	—	—
Gastroenteritis	Infections and infestations	—	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—	—
Ulna fracture	Injury, poisoning and procedural complications	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Mental disorder due to a general medical condition	Psychiatric disorders	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Peripheral embolism	Vascular disorders	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Group 1: Single Dose of Zo…	Group 2: Zostavax - Day 0 …	Group 3: Zostavax - Day 0 …
Injection site erythema	General disorders	—	—	—
Injection site pain	General disorders	—	—	—
Injection site swelling	General disorders	—	—	—
Headache	Nervous system disorders	—	—	—

Most-reported serious reactions: Myocardial infarction, Angina pectoris, Atrial fibrillation, Cardiac failure, Cardiogenic shock, Coronary artery disease, Ileus, Bronchitis.

Data from ClinicalTrials.gov NCT00561080 adverse events section.

Sponsor's own description

Primary objective:

Immunogenicity To demonstrate that a second dose of ZOSTAVAX® elicits higher varicella-zoster virus (VZV) antibody titres than a first dose of ZOSTAVAX® whether given as a 0-1 month schedule or as a 0-3 month schedule in subjects ≥70 years of age as measured at 4 weeks post-vaccination

Secondary objectives Immunogenicity

* To summarise the VZV antibody titres at 4 weeks post-vaccination after a 1-dose regimen and 4 weeks post-vaccination after each dose of each 2-doses regimen of ZOSTAVAX®.
* To compare the VZV antibody titres at 12 months after completion of a 1-dose regimen with the VZV antibody titres at 12 months after completion of each 2-doses regimen of ZOSTAVAX®
* To summarise the VZV antibody titres at 24 and 36 months after completion of a 1-dose regimen and at 24 and 36 months after completion of each 2-doses regimen of ZOSTAVAX®

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: a randomized study of a single dose vs. two different two-dose schedules.
   Vesikari T, Hardt R, Rümke HC, Icardi G, et al · · 2013 · cited 24× · PMID 23319176 · DOI 10.4161/hv.23412