Clinical trial 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)
Official title: An Open-label, Randomised, Comparative, Multi-centre Study of the Immunogenicity and Safety of a 1-dose Regimen and Different 2-dose Regimens of a Zoster Vaccine (Live), ZOSTAVAX ®, in Subjects ≥ 70 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prevention of : Herpes-Zoster
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-11-20
Enrollment: 759
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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®


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 70 years
2. Varicella history-positive or residence for \> 30 years in a country with endemic VZV infection
3. Signed informed consent form prior to any study procedure

Exclusion Criteria:

1. Febrile illness within the last 72 hours before the first vaccination
2. Prior herpes-zoster episode clinically diagnosed by a physician
3. Prior receipt of varicella or zoster vaccine
4. Exposure to varicella or herpes-zoster within the 4 weeks prior to the first vaccination
5. Significant underlying illness preventing completion of the study vaccination schedules,
6. Known active tuberculosis,
7. Immune deficiency disorder, including active neoplastic disease within the prior 5 years,
8. Immune function impairment caused by medical condition or immunosuppressive therapy, or any other cause,
9. Receipt of any inactivated vaccine within the 2 weeks prior to the first vaccination,
10. Receipt of any other live vaccine within the 4 weeks prior to the first vaccination,
11. Receipt of immunoglobulins or blood-derived products within the 5 months prior to the first vaccination,
12. Concomitant use of non-topical antiviral therapy

Primary outcomes:
measure: Geometric Mean Titer (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks After Each Vaccination: Groups 2 and 3
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)
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of VZV Antibodies 4 Weeks After Vaccination: Group 1
timeFrame: 4 weeks post-dose (Month 1)
measure: 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
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)
measure: Geometric Mean Titre of VZV Antibodies 12 Months Post-last Dose
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)
measure: 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
timeFrame: predose 1 and 1 year post-last dose (Group 1: Month 12; Group 2: 13 Month 13; and Group 3: Month 15)
measure: Geometric Mean Titre (GMT) of VZV Antibodies 24 and 36 Months Post-dose 1 in Group 1 and the 24 and 36 Months Post-dose 2 in Groups 2 and 3
timeFrame: 24 and 36 months post-last dose
measure: Geometric Mean Fold Rise (GMFR) in VZV Antibody Titres From Pre-Vaccination To 24 And 36 Months Post-dose 1 in Group 1 and From Pre-vaccination To 24 And 36 Months Post-dose 2 in Groups 2 and 3
timeFrame: Predose 1 and 24 and 36 months post-last dose
measure: Percentage of Participants Who Reported a Solicited Injection Site Reaction : Post-dose 1
timeFrame: up to 4 days after 1st vaccination
measure: Percentage of Participants Who Reported a Solicited Injection Site Reaction: Post-dose 2
timeFrame: up to 4 days after 2nd vaccination
measure: Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 1
timeFrame: up to 28 days after 1st of study drug
measure: Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 2
timeFrame: up to 28 days post-dose 2
measure: Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-dose 1
timeFrame: up to 28 days post-dose 1
measure: Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-Dose 2
timeFrame: up to 28 days post-dose 2
measure: Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 1
timeFrame: up to 28 days post-dose 1
measure: Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 2
timeFrame: up to 28 days post-dose 2
measure: Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 1
timeFrame: up to 28 days after 1st vaccination
measure: Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 2
timeFrame: up to 28 days after 2nd vaccination
measure: Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 1
timeFrame: up to 28 days after 1st vaccination
measure: Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 2
timeFrame: up to 28 days after 2nd vaccination
measure: Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 1
timeFrame: up to 28 days after 1st vaccination
measure: Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 2
timeFrame: up to 28 days after 2nd vaccination
measure: Percentage of Participants Who Reported a Vaccine-related Serious Adverse Event
timeFrame: up to end of study (approximately 15 months)
measure: Percentage of Participants Who Died During the Study
timeFrame: up to end of study (approximately 15 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Hardt R, Rumke HC, Icardi G, Montero J, Thomas S, Sadorge C, Fiquet A. Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax(R)) in individuals aged >/= 70 years: a randomized study of a single dose vs. two different two-dose schedules. Hum Vaccin Immunother. 2013 Apr;9(4):858-64. doi: 10.4161/hv.23412. Epub 2013 Jan 14.