Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: a Phase III, Randomized Clinical Trial.

Clinical Infectious Diseases; 07: 07.

Aims
To investigate the immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy.

Interventions
Patients were randomized to receive either 2 doses of RZV or Placebo 1–2 months apart, 4–18 months post-transplantation.

Participants
264 renal transplant patients (n=132 RZV; n=132 placebo) were enrolled betewen enrolled between March 2014 and April 2017.

Outcomes
Outcomes included anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2.

Follow-up
18 months

CET Conclusions
This is an interesting study of a subunit varicella zoster vaccine in renal transplant recipients. The study was a multicentre, randomised, placebo-controlled trial. It has some indicators of good quality but the report lacks certain details to confirm this. The paper mentions a randomisation algorithm including some “minimisation factors” but there is not enough detail to understand if this was truly random. The study is described as “observer-blind”, but how this was protected is not described. The sample size calculation can be found in the supplemental material, but data are presented throughout the paper without related p-values. The vaccine showed a good humoral response above the thresholds set for immunogenicity, as it also did for cell-mediated responses. The vaccine was associated with more myalgia, shivering and fever than the placebo, but these results are not presented with any statistical test or associated p-value. There does not appear to be any gross difference in renal function, rejection or graft loss after vaccination in this study. Eight of the authors were employees of the GSK group of companies at the time this study was designed, initiated and/or conducted. The study was funded by GSK, who were involved in all stages of the conduct and analysis.

Jadad score
2

Data analysis
Modified intention-to-treat analysis

Allocation concealment
No

Trial registration
ClinicalTrials.gov - NCT02058589

Funding source
Industry funded