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

Phase 1

Completed

Conditions: Herpes Zoster

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

Registration Number: NCT01385566

Lead Sponsor: Merck Sharp & Dohme LLC

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 223

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1/3 Dose Subcutaneous	Intradermal Placebo	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.
1/3 Dose Subcutaneous	ZOSTAVAX™ (Zoster Vaccine Live) 1/3 Dose Subcutaneous	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.
Full Dose Intradermal	ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Intradermal	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.
Full Dose Intradermal	Full Dose Intradermal Placebo	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.
1/3 Dose Intradermal	Intradermal Placebo	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.
Full Dose Subcutaneous	ZOSTAVAX™ (Zoster Vaccine Live) Full Dose Subcutaneous	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.
1/3 Dose Intradermal	ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal	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.
1/10 Dose Intradermal	Intradermal Placebo	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.
Full Dose Subcutaneous	Intradermal Placebo	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.
1/10 Dose Intradermal	ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal	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.
1/27 Dose Intradermal	Intradermal Placebo	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.
1/27 Dose Intradermal	ZOSTAVAX™ (Zoster Vaccine Live) Partial Doses Intradermal	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.

Primary Outcome Measures

Name	Time	Method
Geometric Mean Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Antibodies	Baseline and 6 weeks following vaccine administration	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.
Number of Participants Reporting an Adverse Experience (AE)	Up to 42 days following vaccine administration	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.
Number of Participants Reporting a Serious Adverse Experience (SAE)	Up to 42 days following vaccine administration	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.
Number of Participants Reporting a Serious Adverse Experience	Within 5 days after the blood draw at approximately 20 months following vaccine administration	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
Number of Participants Reporting Specific Local Injection-site Adverse Experiences Prompted for on the Vaccine Report Card (VRC)	Up to 5 days following vaccine administration	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.
Number of Participants Reporting Systemic Adverse Experiences	Up to 42 days following vaccine administration	Systemic AEs included all reported AEs except injection-site AEs
Number of Participants Reporting a Non-injection-site Rash (Varicella, Varicella-like, Herpes Zoster, or Herpes Zoster-like)	Up to 42 days following vaccine administration	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.