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VZV Vaccine for Hematopoietic Stem Cell Transplantation

Phase 2
Completed
Conditions
Varicella Zoster Infection
Interventions
Biological: Zostavax
Biological: Normal Saline
Registration Number
NCT02329457
Lead Sponsor
The University of Hong Kong
Brief Summary

Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients. Most patients will require hospitalization. Despite treatment with high dose acyclovir, patients may develop severe complications including the disabling postherpetic neuralgia, corneal ulceration, viral dissemination and secondary bacterial infection. The median onset of infection is the fifth month following transplantation, with 91% of cases occurring within the first year. Direct vaccination of transplants recipients with subcutaneous live-attenuated VZVv before transplantation and up to one year after transplantation is contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous vaccination for donors before HSCT may offer some protection against VZV reactivation in the recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal microneedle has been shown to elicit a good immunogenic response in both healthy and elderly subjects. We sought to assess the efficacy and safety of the novel intradermal live-attenuated VZVv in sibling donors undergoing HSCT.

Detailed Description

Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients. Most patients will require hospitalization. Despite treatment with high dose acyclovir, patients may develop severe complications including the disabling postherpetic neuralgia, corneal ulceration, viral dissemination and secondary bacterial infection. The median onset of infection is the fifth month following transplantation, with 91% of cases occurring within the first year. Direct vaccination of transplants recipients with subcutaneous live-attenuated VZVv before transplantation and up to one year after transplantation is contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous vaccination for donors before HSCT may offer some protection against VZV reactivation in the recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal microneedle has been shown to elicit a good immunogenic response in both healthy and elderly subjects. We sought to assess the efficacy and safety of the novel intradermal live-attenuated VZVv in sibling donors undergoing HSCT.

We plan to enroll 160 pairs of adult donors and patients who undergo allogeneic HLA matched sibling HSCT in this prospective randomized double-blind placebo-controlled trial over a period of 3 years. Enrolled donors and patients will be randomized into 4 groups: Group 1: intradermal full dose live-attenuated VZVv; Group 2: subcutaneous full dose live-attenuated VZVv; Group 3: intradermal 0.9% normal saline as control; Group 4: subcutaneous 0.9% normal saline as the second control

All vaccines will be given to the donors within 28 days before HSCT. All intradermal vaccines will be given via a microneedle syringe. Both the investigators and participants will be blinded to the randomization process. The primary end point is the occurrence of HZ in the patients within 12 months of transplantation. The secondary end points are the safety and immunological response in the patients and donors.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • patients undergoing allogeneic hemopoietic stem cell transplant
  • HLA identical sibling donors
  • participants willing to provide written informed consents
Exclusion Criteria
  • history of zoster in the 12 months prior to transplantation
  • exposure to VZV within 4 weeks of transplantation
  • neomycin sensitivity
  • sensitivity to any components of the zoster vaccine

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ID varicella zoster vaccine (VZVv) groupZostavaxintradermal 0.65 mL Zostavax
ID NS GroupNormal Salineintradermal 0.65 mL normal saline
SC VZVv groupZostavaxsubcutaneous 0.65 mL Zostavax
SC NS GroupNormal Salinesubcutaneous 0.65 mL normal saline
Primary Outcome Measures
NameTimeMethod
Herpes Zoster Reactivation12 months post transplantation

Incidence of herpes zoster in stem-cell transplant recipients

Secondary Outcome Measures
NameTimeMethod
Immunological response in recipients30, 90, 180 and 360 days post transplantation

Geometric mean concentration of anti-VZV antibody (IU/mL)

Immunological response in donors30, 90, 180 and 360 days post transplantation

Geometric mean concentration of anti-VZV antibody (IU/mL)

Adverse reaction21 days after vaccination

Rate of adverse reaction in donors after vaccination

Trial Locations

Locations (1)

Ivan Hung

馃嚟馃嚢

Hong Kong, Hong Kong

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