ZOSTAVAX® in Renal Transplant Patients
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.
Biological: ZOSTAVAX® (Zoster Vaccine Live)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Phase I Trial of ZOSTAVAX® Prior to Renal Transplantation|
- Biopsy proven graft rejection [ Time Frame: During 12 months post- vaccination or post- transplantation ] [ Designated as safety issue: Yes ]
- Safety: incidence of vaccine related serious adverse events (SAEs). [ Time Frame: During 12 months post- vaccination or post-transplantation ] [ Designated as safety issue: Yes ]
- Safety: any occurrence of proven [polymerase chain reaction (PCR) confirmed] vaccine strain varicella zoster virus (VZV) infection at any site not contiguous with the injection site. [ Time Frame: Entire post-immunization period up to 12 months following transplantation. ] [ Designated as safety issue: Yes ]
- Safety: incidence of grade 3 or higher vaccine related adverse events (AEs) and vaccine related serious adverse events (SAEs). [ Time Frame: During the 4 weeks post-immunization. ] [ Designated as safety issue: Yes ]
- Safety: increase of panel reactive antibody (PRA) by greater than or equal to 10% (e.g., from 10% to 20%) or newly positive donor specific cross match (DXM) after immunization and prior to transplantation in the absence of any other attributable cause. [ Time Frame: Prior to vaccination, following vaccination while on the wait list (for up to 12 months) and at the time of transplantation in those subjects who are transplanted. ] [ Designated as safety issue: Yes ]
- Immune response: changes from baseline number of VZV specific T cells by flow cytometry measuring intracellular interleukin-2 (IL-2), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha after stimulation with VZV antigens. [ Time Frame: Approximately 5 weeks post-immunization, 6 months and 12 months post-immunization or post-transplantation. If transplantation occurs >12 weeks post-vaccination, a repeat pre-transplant baseline is optional. ] [ Designated as safety issue: No ]
- Immune response: changes from baseline glycoprotein-based enzyme-linked immunosorbent assay (gpELISA) varicella zoster virus (VZV) antibody titer. [ Time Frame: Approximately 5 weeks post immunization, 6 months and 12 months post-vaccination or 6 months and 12 months post-transplantation.If transplantation occurs >12 weeks post-vaccination, a repeat pre-transplant baseline is optional. ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
30 subjects to receive 0.65 mL ZOSTAVAX® subcutaneously.
Biological: ZOSTAVAX® (Zoster Vaccine Live)
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 Comparator: Placebo
10 subjects to receive placebo subcutaneously.
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.
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.
|United States, Iowa|
|University of Iowa - Infectious Disease Clinic|
|Iowa City, Iowa, United States, 52242-1009|
|United States, Maryland|
|University of Maryland Baltimore - School of Medicine - Medicine|
|Baltimore, Maryland, United States, 21201-1509|
|United States, Tennessee|
|Vanderbilt University - Medicine - Infectious Diseases|
|Nashville, Tennessee, United States, 37232-2035|