Immunogenicity and Safety Study of ZOSTAVAX Administered by Intramuscular or Subcutaneous Route to Participants Aged From 50 Years Old (V211-045)

Study Overview
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Brief Summary
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PRIMARY OBJECTIVES Two co-primary objectives are: To demonstrate that the immunogenicity of ZOSTAVAX administered by intramuscular route (IM) is non-inferior to ZOSTAVAX administered by subcutaneous route (SC) To demonstrate that ZOSTAVAX administered by IM route induces an acceptable fold-rise of varicella zoster virus (VZV) antibody titre from pre to 4-week post-vaccination SECONDARY OBJECTIVES Immunogenicity objectives To evaluate the immunogenicity as measured by VZV antibody titre at 4 weeks following ZOSTAVAX administered by IM or SC route To evaluate the immune response as measured by a second assay, the VZV Interferon gamma Enzyme-linked immunospot (ELISPOT) at 4 weeks following ZOSTAVAX administered by IM or SC route Safety objective - To describe the safety profile of ZOSTAVAX administered by IM or SC route

Official Title
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An Open-label, Randomised, Comparative, Multicentre Study of the Immunogenicity and Safety of ZOSTAVAX When Administered by Intramuscular Route or Subcutaneous Route to Subjects of 50 Years of Age and Older

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: ZOSTAVAX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged >=50 years Varicella history-positive or residence for >30 years in a country with endemic VZV infection Exclusion Criteria: Febrile illness History of hypersensitivity or anaphylactoid reaction to any of the vaccine components Prior herpes zoster episode clinically diagnosed or exposure to varicella or herpes zoster within the 4 weeks prior to vaccination Prior receipt of varicella or zoster vaccine Active untreated tuberculosis Thrombocytopenia, any other coagulation disorder contraindicating intramuscular injection Receipt of medication / vaccine that may interfere with study assessments Known or suspected immune dysfunction User of recreational / illicit drugs or subject with alcohol abuse or dependence within the last year Any condition that might interfere with the interpretation of the study,

Ages Eligible for Study
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Minimum Age: 50 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: ZOSTAVAX intramuscular (IM) route<br>Single dose of 0.65 mL via IM injection | Biological: ZOSTAVAX<br>* 1 dose 0.65 mL<br>* Other names: V211;|
| Active Comparator: ZOSTAVAX subcutaneous (SC) route<br>Single dose of 0.65 mL via SC injection | Biological: ZOSTAVAX<br>* 1 dose 0.65 mL<br>* Other names: V211;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titre (GMT) of Varicella Zoster Virus (VZV) Antibodies 4 Weeks Post-vaccination | Blood samples taken at 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via Glycoprotein Enzyme Linked Immunosorbent Assay (gpELISA). | 4 week post-vaccination | 
| Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: IM Route | Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-dose/GMT Pre-vaccination | Pre-vaccination (Day 0) and 4 week post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) in VZV Antibody Titre: SC Route | Blood sample taken at predose (Day 0) and 4 weeks post vaccination to determine the geometric mean titre (GMT) of VZV antibodies via gpELISA. The GMFR was calculated as GMT Post-vaccination/GMT Pre-vaccination | Pre-vaccination (Day 0) and 4 week post-vaccination | 
| Geometric Mean Count (GMCs) of VZV Interferon Gamma ((IFN-γ) Enzyme-Linked ImmunoSpot (ELISPOT) Antibodies | Blood samples taken 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMC's. Results were reported as ELISPOT count/10^6 Peripheral Blood Mononuclear Cells (PBMC) | 4 week post-vaccination | 
| Geometric Mean Fold Rise (GMFR) of IFN-γ ELISPOT Antibodies | Blood samples taken pre-vaccination and 4 weeks post-vaccination to determine the IFN-γ ELISPOT GMFR. | Pre-vaccination (Day 0) and 4 week post-vaccination | 
| Percentage of Participants Who Report at Least 1 Injection-site Adverse Reaction | Participants entered data into daily diary card regarding previously identified possible injection site reactions of erythema, injection site swelling or injection site pain for 1st 4 days post-vaccination. Additionally, injection site reactions not prompted on diary card (unsolicited) were collected up 28 days post-vaccination. All injection site reactions (solicited or unsolicited) were recorded. | up to 28 days after vaccination | 
| Percentage of Participants Who Report at Least 1 Systemic Adverse Event | 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. These events included rashes of interest: i.e. Varicella, Varicella-like rashes, Herpes zoster or shingles and Herpes zoster-like rashes and other systemic adverse events. | up to Day 28 after vaccination | 
| Percentage of Participants Who Report at Least 1 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 within 35 days of vaccination were recorded. | up to 35 days after vaccination |