8 - The Adjuvanted Recombinant Zoster Vaccine (RZV) Confers Long-term Protection Against Herpes Zoster: Interim Results of an Extension Study (ZOSTER-049) of Two Clinical Trials (ZOE-50 and ZOE-70)

Background: Two large-scale phase 3 clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]) demonstrated that, in adults ≥ 50 years of age followed over a mean period of 3.1 and 3.7 years respectively, the adjuvanted recombinant zoster vaccine (RZV) was efficacious against herpes zoster (HZ), highly immunogenic and had a clinically acceptable safety profile. In this extension study (ZOSTER-049 [NCT02723773]), RZV-induced immunogenicity persistence and long-term vaccine efficacy (VE) against HZ were evaluated; we report interim results after at least 2 years of follow-up (starting and ending ≈5.1 and 7.1 years, respectively, after initial vaccination during the parent studies).

Methods: The study design is detailed in Figure 1. Primary objective: VE against HZ over the ZOSTER-049 study. Secondary objectives: VE against HZ from 1 month post-dose 2 in ZOE-50/-70 until the end of observation for year (Y)2 of ZOSTER-049, persistence of vaccine-induced humoral immunogenicity (HI) in terms of anti-gE antibody concentrations (by ELISA) and cell-mediated immune (CMI) response in terms of frequency of gE-specific CD4+ T-cells (by intracellular cytokine staining).Figure 1. Study design of the extension study in relation to the parent studies. ZOSTER-049 study procedures, timing, endpoints and cohorts


Results: Of the 7,413 participants enrolled in ZOSTER-049, 7,277 were included in the VE analysis (Figure 2) and 6,972 reached Y2 of this study. The overall VE against HZ during at least 2 years of follow-up in ZOSTER-049 was 84.0% (95% confidence interval [CI]: 75.9–89.8%). From 1 month post-dose 2 in the ZOE-50/-70 studies until the end of observation for Y2 of ZOSTER-049, the overall VE was 90.9% (95% CI: 88.2–93.2%). Anti-gE antibody concentrations persisted ≈6 times above pre-vaccination levels up to Y8 after vaccination (Figure 3A) and the frequency of gE-specific CD4[2+] T-cells remained above baseline from Y6 to Y8 after vaccination (i.e. until the end of observation for Y2 of ZOSTER-049) (Figure 3B).Figure 2. Demographic characteristics of participants included in the ZOSTER-049 study, for the analysis of vaccine efficacy against herpes zoster (mTVC)
Figure 3. Long-term persistence of humoral immunogenicity (HI) and cell-mediated immune (CMI) responses up to year 8 post-vaccination dose 2 administered in the ZOE-50/-70 studies


Conclusion: RZV demonstrated high VE against HZ until the end of the observation period for this Y2 interim analysis. The HI and CMI responses remained stable and high until the end of observation (i.e. 7.1 years after initial vaccination).

Funding: GlaxoSmithKline Biologicals SA
Acknowledgements: LA Truta/S Hulsmans (Modis c/o GSK) provided writing/editorial support

Co-Author(s)

• CB

  Céline Boutry, PhD

  Dr
  Aixial, Bruxelles, Belgium, on behalf of GSK
  Bruxelles, Brussels Hoofdstedelijk Gewest, Belgium

  Disclosure: Aixial (Consultant)

Presenting Author(s)

• 

  Andrew J. Hastie, MD, DipPharmMed

  Senior Clinical Research & Development Lead
  GSK, Rockville, Maryland, United States
  Rockville, Maryland

  Disclosure: GSK group of companies (Employee)

  Slides Slides and Audio

Co-Author(s)

• MS

  Meng Shi, MS

  Expert Statistician
  GSK, Rockville, Maryland, United States
  Rockville, Maryland

  Disclosure: GSK group of companies (Employee)
• JD

  Javier Diez-Domingo, MD

  Head of the Vaccine Research Department
  FISABIO, Valencia, Spain
  Valencia, Comunidad Valenciana, Spain

  Disclosure: GSK group of companies (Board Member, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Board Member, Scientific Research Study Investigator, Advisor or Review Panel member)
• JT

  Juan Carlos Tinoco, MD

  MD
  Hospital General de Durango, Durango, Mexico
  Durango, Durango, Mexico

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CY

  Chong-Jen Yu, MD

  Professor
  National Taiwan University Hospital, Taipei, Taiwan
  Taipei, Taipei

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• PP

  Paola Pirrotta, PharmD

  Expert Safety Scientist
  GSK, Wavre, Belgium
  Wavre, Brabant Wallon, Belgium

  Disclosure: GSK group of companies (Employee)
• GK

  George Kalema, PhD

  Dr
  Keyrus Biopharma, Waterloo, Belgium, on behalf of GSK
  Waterloo, Brabant Wallon, Belgium

  Disclosure: GSK group of companies/Keyrus Biopharma (Consultant)
• AS

  Anne Schuind, MD

  MD
  GSK
  Rockville, Maryland

  Disclosure: GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration)