A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Clinical Trial to Study the Safety, Tolerability, Efficacy, and Immunogenicity of Inactivated Vzv Vaccine (ZVIN) in Recipients of Autologous Hematopoietic Cell Transplants (Auto-Hcts)

Background: Recipients of auto-HCT have an increased risk of Herpes Zoster (HZ) infection and its complications, including postherpetic neuralgia (PHN), secondary bacterial infection, disseminated Varicella Zoster Virus (VZV) infection, hospitalization and occasional mortality. Inactivated VZV Vaccine (ZVIN) is being developed for the prevention and amelioration of HZ and HZ-related complications in patients undergoing auto-HCT. Objectives: Primary objectives were: (1) to assess the safety and tolerability of ZVIN; (2) to assess the impact of ZVIN on the development of HZ following auto-HCT. Methods: Adults (≥18 years old) randomly received either ZVIN (560 subjects), ZVIN high antigen lot (160 subjects), or placebo (564 subjects), administered in a 4-dose regimen. Dose 1 was administered ~30 days prior to HCT. Doses 2 through 4 were administered ~30, ~ 60, and ~90 days post auto-HCT. Randomization was stratified by age (25% for VEHZ. Kaplan-Meier (KM) plot assessed the cumulative incidence rate over time. All subjects who received ≥1 dose of vaccine/placebo and had follow-up data were included in the primary safety analysis. Subjects were monitored for serious adverse experiences (SAE) regardless of causality for the duration of the study. Results: Most HZ cases were confirmed by PCR. None of the VZV rashes were positive for vaccine strain by PCR. The average follow-up time for HZ surveillance in the modified intent to treat (MITT) population was approximately 2.3 years postvaccination. Confirmed HZ occurred in 42 vaccine (n = 538) and 113 placebo (n = 535) recipients. The estimated VEHZ was 63.8%; [95% CI, 48.4% to 74.6%]; adjusted for age and duration of antiviral prophylaxis. The KM plot confirmed the lower cumulative incidence rate of HZ over time in the ZVIN group. The proportions of SAEs and vaccine-related SAEs were similar between the vaccine and placebo groups (32.9% vs. 32.7% [risk difference of .2% (95% CI: −5.1, 5.5)] and .8% vs. .9% [risk difference of -.1% (95% CI: −1.4, 1.1)], respectively). Conclusions: This first-ever presentation of the results of the pivotal Phase III study (V212-001; NCT01229267) demonstrates that ZVIN is efficacious and well-tolerated when administered to adult recipients of auto-HCT.