Immunogenicity and Safety of a Candidate Subunit Adjuvanted Herpes Zoster Vaccine (HZ/su) in Adults Post Renal Transplant: a Phase III Randomized Clinical Trial

Abstract

BackgroundThe incidence rate of herpes zoster (HZ) in individuals with solid organ transplants (SOTs) is estimated as 8–9 times higher than the rate in the overall US population (3.2/1000 person-years). No vaccine is currently available to prevent HZ in immunocompromised individuals. GSK’s HZ/su candidate vaccine, containing varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, has shown >90% efficacy for HZ prevention in immunocompetent adults ≥50 years of age (YOA). We performed a study to determine immunogenicity and safety of HZ/su in adult renal transplant (RT) recipients (RTR) on chronic immunosuppressive therapy; RT was chosen as it can be representative of SOTs due to the nature of administered immunosuppressive therapies.MethodsIn this phase III, observer-blind, multicenter study (NCT02058589), RTRs ≥18 YOA were randomized 1:1 to receive 2 doses of HZ/su or placebo intramuscularly 1–2 months apart. gE-specific vaccine response rates (VRRs) and geometric means (GMs) were assessed for humoral and CD4+ cell-mediated immune (CMI) responses 1 month post dose 2 (M2). Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs and medically-attended AEs (MAEs) for 30 days after each dose. Solicited general and unsolicited AEs were also collected for 7 days prior to dose 1. Potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded until 1 year post dose 2. Data from dose 1 through M2 is presented.ResultsAt M2, 240 subjects (121 HZ/su; 119 placebo) were included in the humoral immunogenicity according-to-protocol (ATP) cohort. All immunogenicity success criteria were met at M2 (Table 1). VRRs for ATP humoral immune cohort and CMI sub-cohort (72 subjects: 36 HZ/su; 36 placebo) were higher in HZ/su groups. Humoral GM concentrations and CMI GM frequencies were significantly higher in HZ/su compared with placebo groups. The frequency of AEs was higher in HZ/su vs. placebo groups for solicited local AEs, but similar for solicited general AEs, unsolicited AEs, MAEs and SAEs. No pIMDs, vaccine-related SAEs or transplant rejections were reported (Table 2).ConclusionHZ/su was highly immunogenic in adults with RT at M2. No safety concerns were identified.FundingGlaxoSmithKline Biologicals SADisclosures P. Vink, GSK group of companies: Employee, Salary and stock options and stock granted