Safety and tolerability of zoster vaccine in adults ≥60 years old

Abstract

Objective

To evaluate the general safety of zoster vaccine (ZV) in adults ≥60 years old.

Patients/Methods

Subjects were enrolled in a 1:1 ratio to receive 1 dose of ZV or placebo. Subjects were followed for serious adverse experiences (SAEs) for 42 days (primary follow-up period) and 182 days (secondary follow-up period) postvaccination. Relative-risks (ZV/placebo) for SAEs during both safety periods were calculated. Study period: 17-Sep‑2007 to 09-Jan-2009.

Results

Overall, 5,983 subjects received ZV and 5,997 received placebo. Within the primary 42-day follow-up period, 84 ZV subjects and 67 placebo subjects reported SAEs. The estimated risk of SAEs within 42 days was 1.41% for ZV versus 1.12% for placebo, with a relative-risk of 1.26 (95% CI 0.91,1.73); indicating no statistically significant difference between groups, meeting the pre-specified success criterion. During the 182-day follow-up period, 340 ZV subjects and 300 placebo subjects reported SAEs. The estimated risk of SAEs within 182 days was 5.68% for ZV versus 5.01% for placebo, with a relative-risk of 1.13 (95% CI 0.98,1.32), indicating no statistically significant difference between groups. Two subjects in the ZV group reported SAEs deemed by the investigator to be vaccine-related (uveitis and sciatica; onset Day 5 and 4, respectively). One subject in the placebo group reported a SAE deemed by the investigator to be vaccine-related (lumbar radiculopathy; onset Day 51). There were 24 fatal SAEs in the ZV group and 17 in the placebo group (relative risk = 1.41; CI: 0.77, 2.60); 6 and 5, respectively, with SAE onset during the primary 42-day follow-up period.  No deaths were deemed vaccine-related.

Conclusions

ZV and placebo groups had similar safety profiles in terms of SAEs during the primary (Day 1 to 42) and secondary (Day 1 to 182) follow-up periods.

Keywords: :

• clinical study
• herpes zoster
• safety
• tolerability
• zoster vaccine

Acknowledgments

The authors would like to thank:All the subjects who participated in this study, ICON Clinical Research (North Wales, PA, and Eastleigh, UK) for study conduct, and Data Monitoring Committee Members for study oversight

Financial Disclosure

Other than employees of Merck (as indicated on the title page), all authors have been investigators for the sponsor. KSR has also received speaker fees and consultancy payments from the sponsor. Employees may hold stock and/or stock options in the company.

Author Contributions

Murray, Reisinger, and Kerzner: enrollment of subjects and/or data collection, analysis and interpretation of data, and preparation of manuscript. Stek, Sausser, Xu, and Parrino: analysis and interpretation of data, and preparation of manuscript. Chan, Wang, and Annunziato: study concept and design, analysis and interpretation of data, and preparation of manuscript. The report was primarily drafted by Murray, Stek, and Parrino. All co-authors approved the final version of the manuscript.

Sponsor’s Role

This study was funded by Merck Sharp and Dohme Corp. (sponsor). In conjunction with the external investigators, this study was designed, executed, and analyzed by the sponsor. Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript.

ZOSTAVAX^® Protocol 020 Study Group

C. Albert (Niedersachsen, Germany), C. Andrews (San Antonio, TX), R. Biedenbender (Norfolk, VA), K. Charani (Tucson, AZ), H. Charles (ElyCardiff, UK), S. Christensen (Salt Lake City, UT), D. DeSantis (Tempe, AZ), D. Dinh (Garden Grove, CA), A. Dowell (Point Claire, Quebec), J. Ervin (Kansas City, MO), M. Eyck (Berlin, Germany), L. Ferguson (Truro, Nova Scotia), T. Fiel (Tempe, AZ), D. Fried (Warwick RI), J. Goehas (Chicago, IL), L. Gilderman (Pembroke Pines, FL), D. Haworth (Lancashire, UK), L. Helman (South Bend, IN), D. Henry (Salt Lake City, UT), B. Kerzner (Baltimore, MD), J. Kirstein (West Jordan, UT), J. Lawless (Camillus, NY), P. Lee (Houston, TX), L. Martínez (Barcelona, Spain), D. Morin (Bristol, TN), A. Murray (Greensboro, NC), L. Murray (Pinellas Park, FL), K. Reisinger (Pittsburgh, PA), S. Rodstein (Edina, MN), J. Rosen (Miami, FL), J. Rubino (Raleigh, NC), N. Sandoval (Tucson, AZ), D. Schadendorf (Baden-Württemberg, Germany), K. Schmader (Durham, NC), B. Seidman (Delray Beach, FL), S. Shapr (Nashville, TN), R. Sharma (East Sussex, UK), G. Shockey (Mesa AZ), C. Strout (Mt. Pleasant, SC), M. Terns (Barcelona, Spain), M. Turner (Boise, ID), S. Tyring (Houston, TX), M. Van Cleeff (Cary, NC), V. von Behren (Hessen, Germany), C. Woodruff (Birmington, AL), P. Zickler (Surrey, BC)