ZOSTAVAX® in Renal Transplant Patients
Condition: Herpes Zoster
MeSH terms: Herpes Zoster
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety of a licensed zoster vaccine, ZOSTAVAX®
      (Zoster Vaccine Live) in 40 subjects, age 18 years or older, with chronic kidney disease
      (CKD) who are scheduled to receive a living donor kidney transplant. ZOSTAVAX® is not
      licensed for use in immunosuppressed persons and in the United States for individuals less
      than 50 years of age. Subjects will receive either ZOSTAVAX® vaccine or placebo (inactive
      substance) no less than 4 weeks prior to their kidney transplant. Study procedures include:
      physical exam, blood samples and documentation of daily temperatures and/or side effects in a
      diary following vaccination. Participants may be involved in study related procedures for up
      to 18 months.
    

Detailed description: 
      Infection with varicella-zoster virus (VZV) produces a life-long latent infection in sensory
      ganglia. Reactivation of viral replication from latency results in a number of clinical
      syndromes, most commonly herpes zoster, or shingles. Herpes zoster is typically a unilateral
      vesicular rash in a dermatomal distribution accompanied by radicular pain that may be severe.
      Immunocompromised persons are at higher risk for herpes zoster than immunocompetent adults.
      The markedly increased risk of herpes zoster in organ transplant recipients suggests that
      this population would benefit substantially if a similar strategy could be adopted. The
      currently licensed zoster vaccine, ZOSTAVAX® (Zoster Vaccine Live), is not licensed for use
      in immunosuppressed persons and in the United States for those less than 50 years of age. A
      small Phase I study is important to address immunogenicity in patients with Chronic Kidney
      Disease (CKD) prior to transplantation as well as safety and persistence of immune responses
      following transplantation. This study is a multi-center, double blind, randomized,
      placebo-controlled trial of ZOSTAVAX® immunization in subjects who will undergo renal
      transplantation from a living donor or are wait-listed for a deceased donor no less than 4
      weeks prior to transplantation. The primary objective of this study is to assess the safety
      of ZOSTAVAX® when administered to subjects with CKD a minimum of 4 weeks prior to live donor
      renal transplantation. This will be accomplished by comparing the rates of specific local and
      systemic reactogenicity events and adverse events (AEs) between the vaccine and placebo
      groups. Subjects likely to be suitable for renal transplant and who have an identified living
      donor will be consented for screening serology for antibodies to VZV if such serology is not
      standard of care or serostatus is not known. Subjects with positive VZV serology, an
      identified living donor, and meeting inclusion and exclusion criteria will provide signed
      informed consent for study enrollment. Subjects will be randomized to receive either active
      vaccine (ZOSTAVAX®) [30 subjects] or placebo vaccine [10 subjects]. Blood will be drawn on
      day 0 (day of vaccine) prior to vaccine administration for assessment of baseline humoral and
      cellular immunity to VZV. Subjects will receive ZOSTAVAX® or placebo vaccination. At
      approximately 5 weeks post-vaccination, subjects will have blood drawn for measurement of
      humoral and cellular immune response. Subjects will undergo living donor renal transplant
      with immunosuppression according to standard of care at each institution. All transplanted
      subjects will receive anti-viral prophylaxis for 3 months post-transplant, consisting of
      either valganciclovir (or ganciclovir) or acyclovir (or valacyclovir or famciclovir)
      depending on risk of cytomegalovirus (CMV) disease. Subjects will be followed and treated by
      the renal transplant team at each center according to local standard of care with concomitant
      monitoring by the vaccine study teams. Subjects will have blood drawn for humoral and
      cell-mediated immune assays at day 0, and week 5 post vaccination, and 6 months and 12 months
      post-transplantation if they undergo transplantation. Parent protocol to sub-study 09-0025.
    

Intervention name(s): Live attenuated herpes zoster vaccine; Placebo
Intervention type(s): Biological; Other
Intervention description(s): ZOSTAVAX® (Zoster Vaccine Live) is a live attenuated vaccine provided as a single-dose, sterile, lyophilized, preservative-free frozen formulation. The vaccine will be supplied in 3-mL glass vials. Sterile diluent will be used to reconstitute study vaccine. The reconstituted vial will be gently agitated to mix thoroughly. The entire contents of the reconstituted vaccine vial (approximately 0.65 mL) will be withdrawn into a syringe. The vaccine will be administered immediately subcutaneously in the deltoid region.; Placebo for Zoster Vaccine Live (ZOSTAVAX®) is sterile normal saline which will be obtained from the Fisher Repository in single-dose containers. 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. The placebo will be administered subcutaneously in the deltoid region.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: immunocompromised,parent protocol,shingles,varicella-zoster virus,ZOSTAVAX®