A Study of Intradermal Administration of ZOSTAVAX™ (V211-051 AM2)

Study Overview
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Brief Summary
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This study will compare the safety and immunogenicity of ZOSTAVAX™ (V211) administered both intradermally and subcutaneously at various doses.

Detailed Description
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This is an exploratory, randomized, partially blinded, multicenter clinical study designed to compare safety and biomarkers of varicella zoster virus immunogenicity when administering ZOSTAVAX™ (V211) at various doses both intradermally and subcutaneously in healthy male and female participants 50 years of age and older.

Official Title
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A Partially Blinded Randomized Clinical Trial to Study the Immunogenicity and Safety of Intradermal Administration of ZOSTAVAX™ (V211)

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Subcutaneous
* Biological: ZOSTAVAX™ (Zoster Vaccine Live) 1/3 Dose Subcutaneous
* Biological: ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Intradermal
* Biological: ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal
* Biological: Full Dose Intradermal Placebo
* Biological: Intradermal Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior history of varicella (chickenpox) or residence in a country with endemic varicella zoster virus infection for at least 30 years Temperature less than 100.4 °F on day of vaccination Female participants of reproductive potential must have a negative pregnancy test and agree to remain abstinent or use two acceptable contraceptive methods for 3 months postvaccination In good health Exclusion Criteria: History of hypersensitivity reaction to any vaccine component, including gelatin or neomycin Household exposure to pregnant women who have not had chickenpox and have not been vaccinated against varicella or to immunosuppressed/immunodeficient individuals Household or workplace exposure to children 18 months and younger who have not been vaccinated against varicella Prior history of herpes zoster Prior receipt of any varicella or zoster vaccine Received or is expected to receive immune globulin and/or blood products from 5 months prior to randomization through 42 days after vaccination On immunosuppressive therapy Known or suspected immune dysfunction Received a live virus vaccine or is scheduled to receive a live virus vaccine from 4 weeks prior to study vaccination through the completion of all study visits Received any inactivated vaccine or is scheduled to receive any inactivated vaccine from 7 days prior to study vaccination through 7 days postvaccination, except for inactivated influenza vaccine Not ambulatory Pregnant or breastfeeding Use of nontopical antiviral therapy with activity against herpes viruses Active untreated tuberculosis

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Full Dose Subcutaneous<br>Participants will receive a full dose of ZOSTAVAX™ administered subcutaneously on Day 1 of the study. Nine participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Subcutaneous<br>* One 0.65 mL injection subcutaneously on Day 1<br>* Other names: V211;Biological: Intradermal Placebo<br>* One intradermal placebo injection of approximately 0.1 mL on Day 1<br>|
| Experimental: 1/3 Dose Subcutaneous<br>Participants will receive a 1/3 dose of ZOSTAVAX™ administered subcutaneously on Day 1 of the study. Six participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. Participants will have the option to receive a full subcutaneous dose of ZOSTAVAX™ after completion of the study. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) 1/3 Dose Subcutaneous<br>* One approximately 0.22 mL injection subcutaneously on Day 1<br>* Other names: V211;Biological: Intradermal Placebo<br>* One intradermal placebo injection of approximately 0.1 mL on Day 1<br>|
| Experimental: Full Dose Intradermal<br>Participants will receive a full dose of ZOSTAVAX™ administered intradermally on Day 1 of the study. Six participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. Participants will have the option to receive a full subcutaneous dose of ZOSTAVAX™ after completion of the study. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Intradermal<br>* Two intradermal injections of approximately 0.15 mL each on Day 1<br>* Other names: V211;Biological: Full Dose Intradermal Placebo<br>* Two intradermal placebo injections of approximately 0.15 mL each on Day 1<br>|
| Experimental: 1/3 Dose Intradermal<br>Participants will receive a 1/3 dose of ZOSTAVAX™ administered intradermally on Day 1 of the study. Six participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. Participants will have the option to receive a full subcutaneous dose of ZOSTAVAX™ after completion of the study. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal<br>* One intradermal injection of approximately 0.1 mL on Day 1<br>* Other names: V211;Biological: Intradermal Placebo<br>* One intradermal placebo injection of approximately 0.1 mL on Day 1<br>|
| Experimental: 1/10 Dose Intradermal<br>Participants will receive a 1/10 dose of ZOSTAVAX™ administered intradermally on Day 1 of the study. Six participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. Participants will have the option to receive a full subcutaneous dose of ZOSTAVAX™ after completion of the study. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal<br>* One intradermal injection of approximately 0.1 mL on Day 1<br>* Other names: V211;Biological: Intradermal Placebo<br>* One intradermal placebo injection of approximately 0.1 mL on Day 1<br>|
| Experimental: 1/27 Dose Intradermal<br>Participants will receive a 1/27 dose of ZOSTAVAX™ administered intradermally on Day 1 of the study. Six participants in this group will also receive saline placebo intradermally in the alternate limb on Day 1. Participants will have the option to receive a full subcutaneous dose of ZOSTAVAX™ after completion of the study. | Biological: ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal<br>* One intradermal injection of approximately 0.1 mL on Day 1<br>* Other names: V211;Biological: Intradermal Placebo<br>* One intradermal placebo injection of approximately 0.1 mL on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Antibodies | VZV antibody titers were measured by glycoprotein enzyme-linked immunosorbent assay at baseline and at 6 weeks after vaccine administration. The geometric mean fold change represents the 6-week value / the baseline value. | Baseline and 6 weeks following vaccine administration | 
| Number of Participants Reporting an Adverse Experience (AE) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse experience. | Up to 42 days following vaccine administration | 
| Number of Participants Reporting a Serious Adverse Experience (SAE) | An SAE is any adverse experience that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect in offspring of a study participant, is a cancer, or is another important medical event when, based on appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention. | Up to 42 days following vaccine administration | 
| Number of Participants Reporting a Serious Adverse Experience | An SAE is any adverse experience that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect in offspring of a study participant, is a cancer, or is another important medical event when, based on appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention | Within 5 days after the blood draw at approximately 20 months following vaccine administration | 
| Number of Participants Reporting Specific Local Injection-site Adverse Experiences Prompted for on the Vaccine Report Card (VRC) | The VRC actively prompts for local injection-site AEs of redness, swelling, and pain/tenderness and for the size of local injection-site reactions of redness and swelling that occur within 5 days of vaccination. The presence of varicella/varicella-like rash and herpes zoster/herpes zoster-like rash is also captured on the VRC. Participants receiving an injection in both limbs will be instructed to complete injection-site reaction information for each limb. All injection-site AEs were reported for the limb in which they occurred: V211 vaccine or placebo. | Up to 5 days following vaccine administration | 
| Number of Participants Reporting Systemic Adverse Experiences | Systemic AEs included all reported AEs except injection-site AEs | Up to 42 days following vaccine administration | 
| Number of Participants Reporting a Non-injection-site Rash (Varicella, Varicella-like, Herpes Zoster, or Herpes Zoster-like) | Non-injection-site rashes were examined by a study physician. Rashes suspected to be varicella/varicella-like or herpes zoster/herpes zoster-like were sampled for verification by polymerase chain reaction. | Up to 42 days following vaccine administration |