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)

Study Overview
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Brief Summary
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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®

Official Title
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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

Conditions
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Prevention of : Herpes-Zoster

Intervention / Treatment
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* Biological: Zostavax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 70 years Varicella history-positive or residence for > 30 years in a country with endemic VZV infection Signed informed consent form prior to any study procedure Exclusion Criteria: Febrile illness within the last 72 hours before the first vaccination Prior herpes-zoster episode clinically diagnosed by a physician Prior receipt of varicella or zoster vaccine Exposure to varicella or herpes-zoster within the 4 weeks prior to the first vaccination Significant underlying illness preventing completion of the study vaccination schedules, Known active tuberculosis, Immune deficiency disorder, including active neoplastic disease within the prior 5 years, Immune function impairment caused by medical condition or immunosuppressive therapy, or any other cause, Receipt of any inactivated vaccine within the 2 weeks prior to the first vaccination, Receipt of any other live vaccine within the 4 weeks prior to the first vaccination, Receipt of immunoglobulins or blood-derived products within the 5 months prior to the first vaccination, Concomitant use of non-topical antiviral therapy

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose of Zostavax<br>Zostavax 0.65mL intramuscular injection administered on Day 0 | Biological: Zostavax<br> <br> * Other names: Zoster vaccine live;|
| Experimental: Zostavax - Day 0 and Month 1<br>Zostavax 0.65mL intramuscular injection administered on Day 0 and Month 1 | Biological: Zostavax<br> <br> * Other names: Zoster vaccine live;|
| Experimental: Zostavax - Day 0 and Month 3<br>Zostavax 0.65mL intramuscular injection administered on Day 0 and Month 3 | Biological: Zostavax<br> <br> * Other names: Zoster vaccine live;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks After Each Vaccination: Groups 2 and 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). | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of VZV Antibodies 4 Weeks After Vaccination: Group 1 | Blood sample taken at 4 weeks post vaccination to determine the geometric mean titer (GMT) of VZV antibodies via gpELISA. | 4 weeks post-dose (Month 1) | 
| 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 | 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 | 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) | 
| Geometric Mean Titre of VZV Antibodies 12 Months Post-last Dose | Blood sample taken at 1 year post last vaccination to determine the geometric mean titer (GMT) of varicella antibodies via gpELISA. | 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) | 
| 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 | 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. | predose 1 and 1 year post-last dose (Group 1: Month 12; Group 2: 13 Month 13; and Group 3: Month 15) | 
| 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 | Blood sample taken at 36 months post last-vaccination to determine the geometric mean titer (GMT) of varicella antibodies via gpELISA. | 24 and 36 months post-last dose | 
| 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 | 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. | Predose 1 and 24 and 36 months post-last dose | 
| Percentage of Participants Who Reported a Solicited Injection Site Reaction : Post-dose 1 | Participants entered data into daily dairy card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain | up to 4 days after 1st vaccination | 
| Percentage of Participants Who Reported a Solicited Injection Site Reaction: Post-dose 2 | Participants entered data into daily dairy card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain | up to 4 days after 2nd vaccination | 
| Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: Post-dose 1 | 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. | up to 28 days after 1st of study drug | 
| Percentage of Participants Who Reported an Unsolicited Injection Site Reaction: 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. | up to 28 days post-dose 2 | 
| Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-dose 1 | Percentage of participants who reported herpes zoster or zoster-like rash following the 1st dose of vaccine were recorded. | up to 28 days post-dose 1 | 
| Percentage of Participants Who Reported Herpes Zoster or Zoster-like Rash: Post-Dose 2 | Percentage of participants who reported herpes zoster or zoster-like rash following the 2nd dose of vaccine were recorded. | up to 28 days post-dose 2 | 
| Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 1 | Percentage of participants that reported varicella or varicella-like rash following the 1st dose of vaccine were recorded. | up to 28 days post-dose 1 | 
| Percentage of Participants Who Reported Varicella or Varicella-like Rash: Post-dose 2 | Percentage of participants that reported varicella or varicella-like rash following the 2nd dose of vaccine were recorded. | up to 28 days post-dose 2 | 
| Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 1 | 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 | up to 28 days after 1st vaccination | 
| Percentage of Participants Who Reported a Systemic Adverse Event: Post-dose 2 | 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, | up to 28 days after 2nd vaccination | 
| Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 1 | 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 | up to 28 days after 1st vaccination | 
| Percentage of Participants Who Reported a Vaccine-related Systemic Adverse Event: Post-dose 2 | 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, | up to 28 days after 2nd vaccination | 
| Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 1 | 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. | up to 28 days after 1st vaccination | 
| Percentage of Participants Who Reported a Serious Adverse Event: Post-dose 2 | 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. | up to 28 days after 2nd vaccination | 
| Percentage of Participants Who Reported a Vaccine-related Serious Adverse Event | 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. | up to end of study (approximately 15 months) | 
| Percentage of Participants Who Died During the Study | The number of participants who died for any reason during the study was summarized. | up to end of study (approximately 15 months) |