Study to Evaluate Immunogenicity, Safety, and Tolerability of ZOSTAVAX™ Vaccine (Zoster Vaccine Live, V211) Administered Concomitantly Versus Nonconcomitantly With Quadrivalent Influenza Virus Vaccine (Inactivated) in Participants ≥50 Years of Age (V211-062)

Study Overview
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Brief Summary
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The study evaluated immunogenicity, safety, and tolerability of ZOSTAVAX™ Vaccine (V211) administered concomitantly versus nonconcomitantly with Quadrivalent Influenza Virus vaccine (inactivated) in participants ≥50 years of age. The primary hypotheses tested 1) the noninferiority of concomitant versus nonconcomitant vaccination with regard to Varicella zoster virus (VZV) Geometric Mean Titer (GMT) antibody responses, 2) the acceptability of geometric mean fold rise in VZV antibody response after concomitant vaccination, and 3) the noninferiority of concomitant versus nonconcomitant vaccination with regard to influenza virus strain-specific GMT antibody responses.

Official Title
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A Phase III, Double-Blind, Randomized, Multicenter Study to Evaluate the Immunogenicity, Safety, and Tolerability of ZOSTAVAX™ Administered Concomitantly Versus Nonconcomitantly With Quadrivalent Influenza Virus Vaccine (Inactivated)

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: ZOSTAVAX™
* Biological: Placebo to ZOSTAVAX™
* Biological: Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has history of varicella or residence in a VZV-endemic area for ≥30 years Is male, female not of reproductive potential, or female of reproductive potential and has a negative pregnancy test and agrees to avoid becoming pregnant throughout the study Exclusion Criteria: Has history of hypersensitivity to any vaccine component Has previously received any varicella or zoster vaccine Has received an influenza vaccine for the 2015-16 season Has history of Herpes zoster Has received immunoglobulin, monoclonal antibodies, or any blood products within 5 months before study vaccination Is pregnant or breastfeeding, or expecting to conceive during the study Has used immunosuppressant therapy Has known or suspected immune dysfunction Has experienced Guillain-Barré syndrome within 6 weeks Has severe thrombocytopenia or any other coagulation disorder

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concomitant Vaccination<br>ZOSTAVAX™ concomitantly with influenza vaccine on Day 1, placebo to ZOSTAVAX™ at Week 4 | Biological: ZOSTAVAX™<br>* A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (concomitant) or at Week 4 (nonconcomitant)<br>* Other names: V211;Biological: Placebo to ZOSTAVAX™<br>* A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (nonconcomitant) or at Week 4 (concomitant)<br>Biological: Influenza Vaccine<br>* A single open-label administration of 0.5 mL intramuscular injection on Day 1<br>* Other names: Fluzone, Vaxigrip;|
| Experimental: Nonconcomitant Vaccination<br>Influenza vaccine and placebo to ZOSTAVAX™ on Day 1, ZOSTAVAX™ at Week 4 | Biological: ZOSTAVAX™<br>* A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (concomitant) or at Week 4 (nonconcomitant)<br>* Other names: V211;Biological: Placebo to ZOSTAVAX™<br>* A single blinded administration of 0.65 mL subcutaneous injection on Day 1 (nonconcomitant) or at Week 4 (concomitant)<br>Biological: Influenza Vaccine<br>* A single open-label administration of 0.5 mL intramuscular injection on Day 1<br>* Other names: Fluzone, Vaxigrip;|

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) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody | Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group. | Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group) | 
| Geometric Mean Fold Rise From Baseline in VZV gpELISA Antibody Titers | Anti-VZV antibodies were determined using a Glycoprotein Enzyme-linked Immunosorbent Assay. Baseline was Day 1 for the Concomitant group and Week 4 for the Nonconcomitant group. | Baseline and 4 weeks after ZOSTAVAX™ vaccination (Week 4 for Concomitant group and Week 8 for Nonconcomitant group) | 
| Geometric Mean Titers of H1N1-specific Influenza Virus Antibody | Antibodies to H1N1-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. | Baseline and 4 weeks after Influenza vaccination (Week 4) | 
| Geometric Mean Titers of H3N2-specific Influenza Virus Antibody | Antibodies to H3N2-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. | Baseline and 4 weeks after Influenza vaccination (Week 4) | 
| Geometric Mean Titers of B-Yamagata-specific Influenza Virus Antibody | Antibodies to B-Yamagata-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. | Baseline and 4 weeks after Influenza vaccination (Week 4) | 
| Geometric Mean Titers of B-Victoria-specific Influenza Virus Antibody | Antibodies to B-Victoria-specific influenza virus hemagglutinin were measured using a Hemagglutinin Inhibition (HAI) assay. Antibody titers are the reciprocal of the highest dilution of serum that completely inhibited hemagglutinin. | Baseline and 4 weeks after Influenza vaccination (Week 4) |