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

BACKGROUND: The 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 AS01(B) 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. METHODS: In 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. RESULTS: At 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). CONCLUSION: HZ/su was highly immunogenic in adults with RT at M2. No safety concerns were identified. FUNDING: GlaxoSmithKline Biologicals SA DISCLOSURES: P. Vink, GSK group of companies: Employee, Salary and stock options and stock granted