A Study to Evaluate Immunity to Varicella Zoster Virus After Immunization With V212 Vaccine or Zostavax (V212-003)

Study Overview
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Brief Summary
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A study in two parts (Part A and Part B) to evaluate the responsiveness of various biomarkers of immunity to Varicella-Zoster Virus (VZV) following repeated immunizations with heat treated VZV vaccine V212 or with Zostavax™. The enrollment of participants into this study was conducted in 2 parts, Part A and Part B. The first 42 eligible participants were enrolled into Part A of the study. In Part A, the reaction of the VZV skin test at baseline was evaluated at both 48 and 72 hours post administration of the VZV skin test reagent and saline (in opposite arms), with 2 examiners performing the reading at each timepoint; all subsequent skin test readings in Part A were performed at 48 hours post administration. After all skin test reactions were obtained at baseline for the 42 subjects in Part A, an interim analysis was performed (1) to assess the frequency of baseline negative skin tests in order to confirm that the planned sample size (N=120) was adequate for an evaluation of the effect of vaccination on the VZV Skin Test, and (2) to assess the frequency of baseline positive skin tests at 72 hours relative to 48 hours (post administration) in order to determine the preferred time for evaluation of the skin test reaction. The interim analysis from Part A confirmed the study sample size, an additional 78 subjects were enrolled into Part B to achieve the planned sample size (N=120). The study procedures for Part B of the study were identical to those in Part A with the following exceptions: (1) baseline skin test readings were performed only once, at either 48 or 72 hours (post administration) to accommodate the scheduling of clinic visits, and (2) only one examiner was needed for the skin test reading at baseline.

Detailed Description
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All eligible participants, regardless of treatment group, were administered three injections of the varicella antigen (VZV Skin Test reagent), once at baseline before the first vaccination, a second time before the second vaccination, and a third time approximately 14 days after the second vaccination. Reactions to the skin test were assessed by the same examiner for each participant to the greatest extent possible.

Official Title
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A Double-Blind, Randomized, Placebo Controlled, Parallel Group Study to Evaluate Biomarkers of Immunity to Varicella Zoster Virus Following Immunization With V212/Heat-Treated Varicella-Zoster Virus (VZV) Vaccine or With ZOSTAVAX in Healthy Volunteers

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: V212
* Biological: Comparator: Zostavax™
* Biological: Comparator: Placebo
* Other: VZV Skin Test
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has prior history of Varicella Female participants are of non-childbearing potential Exclusion Criteria: Participant has had a hypersensitivity reaction to any vaccine component Participant has a prior history of Herpes Zoster Participant has received any Varicella or Zoster vaccine including Zostavax Participant has a history of immunosuppression caused by disease, corticosteroids, cancer therapy or organ transplant Participant has an active cancer Participant has received or will receive a live virus vaccine or an inactivated virus vaccine 4 weeks prior to participating in study (with the exception of influenza vaccine) Participant is not bed-ridden or homebound

Ages Eligible for Study
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Minimum Age: 60 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V212<br>Participants randomized to receive V212 (heat treated VZV Vaccine) | Biological: V212<br>* Two doses of 0.65 mL V212 subcutaneous injection administered at Day 1 and Day 31<br>Other: VZV Skin Test<br>* Three intradermal injections of the 0.1 ml varicella antigen (VZV Skin Test reagent) were administered, once at baseline before the first vaccination, a second time before the second vaccination, and a third time approximately 14 days after the second vaccination.<br>Other: Saline<br>* One intradermal injection of the 0.1 ml saline was administered at the time of the baseline VZV skin test prior to the first vaccination. Saline and VZV skin test reagents were administered on opposite arms.<br>|
| Active Comparator: Zostavax™<br>Participants randomized to receive Zostavax™ (Zoster Vaccine, live) | Biological: Comparator: Zostavax™<br>* Two doses of 0.65 mL Zostavax™ subcutaneous injection administered at Day 1 and Day 31<br>* Other names: V211 (Zoster Vaccine Live (Oka/Merck));Other: VZV Skin Test<br>* Three intradermal injections of the 0.1 ml varicella antigen (VZV Skin Test reagent) were administered, once at baseline before the first vaccination, a second time before the second vaccination, and a third time approximately 14 days after the second vaccination.<br>Other: Saline<br>* One intradermal injection of the 0.1 ml saline was administered at the time of the baseline VZV skin test prior to the first vaccination. Saline and VZV skin test reagents were administered on opposite arms.<br>|
| Placebo Comparator: Placebo<br>Participants randomized to receive placebo | Biological: Comparator: Placebo<br>* Two doses of 0.65 mL subcutaneous injection of placebo administered at Day 1 and Day 31<br>Other: VZV Skin Test<br>* Three intradermal injections of the 0.1 ml varicella antigen (VZV Skin Test reagent) were administered, once at baseline before the first vaccination, a second time before the second vaccination, and a third time approximately 14 days after the second vaccination.<br>Other: Saline<br>* One intradermal injection of the 0.1 ml saline was administered at the time of the baseline VZV skin test prior to the first vaccination. Saline and VZV skin test reagents were administered on opposite arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Negative VZV Skin Test at Baseline (Part A) | Participants were given the VZV skin test prior to vaccination. For the baseline VZV skin test, they were administered VZV skin test reagent and saline in opposite arms, and assessed for a skin reaction around the injection site. The skin reaction assessed was erythema (redness of skin) and induration (palpable, raised, hardened area) around the injection site, which was marked with a ball point pen. The longest dimension to the closest 1 mm was measured. Participants with a reaction measure < 5mm for saline and < 5mm for the VZV antigen were considered to have a negative baseline skin test. | 48 hours following administration of the baseline skin test | 
| Number of Healthy, Elderly, Immunocompetent Participants With a Positive VZV Skin Test After Administration of 2 Doses of V212 Vaccine (Part B) | Number of participants with a positive VZV skin test after 2 vaccine doses was determined. Participants with a negative VZV skin test reaction at baseline were evaluated for VZV immunogenicity by a final VZV skin test administered 14 days after dose 2 of vaccination. For the VZV skin test participants were injected intradermally with the VZV skin test reagent, and reaction to the skin test was assessed after 48-72 hrs. A skin reaction (erythema and induration) around the injection site measuring >= 5mm for the VZV antigen was considered a positive skin test. | 48-72 hours after administration of skin test at 14-17 days postdose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VZV Skin Test Reactions at 48 and 72 Hours (Part A) | Prior to vaccination, participants were administered a baseline VZV skin test for which the skin test reagent and saline were injected in opposite arms. The skin reaction (erythema and induration) around the injection site was assessed at 48 hours and at 72 hours. The reaction was marked with a ball point pen and the longest dimension closest to 1 mm was measured. Participants with a reaction measure < 5mm for saline and < 5mm for the VZV antigen were defined as having a negative baseline skin test; and a measure of >= 5mm for the VZV antigen were defined as having a positive skin test. | 48 hours and 72 hours post administration of baseline skin test | 
| Number of Healthy Elderly Men and Women With Adverse Events Post Vaccination With V212 (Part B) | The number of participants with all serious and nonserious adverse events, and vaccine-related serious and nonserious adverse events, from 1-28 days post any vaccination dose was determined to assess safety. Non serious adverse events include injection-site adverse events as well as systemic adverse events post vaccination. Vaccine-related events include all events that were possibly, probably or definitely related to the vaccine according to the investigator. Participants with injection site adverse events due to administration of VZV skin tests are not included. | 1-28 days post vaccination dose 1 and 1-28 days post vaccination dose 2 | 
| Number of Healthy Elderly Men and Women With Injection Site Adverse Events Post Administration of VZV Skin Tests (Part B) | The number of participants with injection site adverse events due to the VZV skin test after administration of the VZV skin test antigen. | 1-5 days post administration of each VZV skin test |