A Double-Blind, Randomized, Controlled, Multicenter Safety and Immunogenicity Study of a Refrigerator-Stable Formulation of ZOSTAVAX®

University Clinical Research, Pembroke Pines, FL, FFM Clinical Research, Camillus, NY, Tomac, Inc., Columbiana, AL, Clinical Vaccines and Biologics, Merck and Co., Inc., West Point, PA, Medical Communications, Merck and Co., Inc., West Point, PA, Clinical Biostatistics, Merck and Co., Inc., West Point, PA

^* To whom correspondence should be addressed. Email: jeffrey_silber{at}merck.com.

	Abstract

Background: ZOSTAVAX® has been shown to prevent herpes zoster (HZ) and postherpetic neuralgia (PHN) and is recommended for individuals 60 years of age. This study compared safety and immunogenicity of a refrigerator-stable formulation (ZOSTAVAX® Refrigerated) with the current formulation (ZOSTAVAX® Frozen) in subjects 50 years of age.

Methods: HZ history-negative subjects were randomized 1:1 to receive one dose of either formulation. Enrollment was stratified 1:2 by age (50 to 59 years; 60 years). Safety was evaluated for 28 days postvaccination. Varicella-zoster virus (VZV) antibody responses were measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA). Primary endpoints were VZV antibody geometric mean titer (GMT; Day 28) and geometric mean foldrise (GMFR; Day 1 to 28), and the incidence of vaccine-related serious adverse experiences (AEs) over 28 days.

Results: The refrigerated (N=182) and frozen (N=185) formulations induced similar GMTs (727.4 and 834.4 gpELISA units/mL, respectively); the estimated GMT ratio [Refrigerated/Frozen] was 0.87 [95% CI = 0.71, 1.07]. The GMFRs were 2.6 and 2.9, respectively. No vaccine-related serious AEs were reported in either group and the safety profiles of the formulations were generally similar. Frequencies of injection-site AEs during follow-up were 35.6% and 46.4%, in the refrigerated and frozen formulation groups, respectively, and were generally mild. Frequencies of systemic AEs were similar and of vaccine-related AE's were 6% in both groups.

Conclusion: The refrigerator-stable formulation of ZOSTAVAX® has an acceptable safety profile, is as immunogenic as the frozen formulation, and will allow use of the vaccine in clinical settings where freezer availability is limited.