VZV Vaccine for Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of a Novel Intradermal Live-attenuated Varicella Zoster Vaccine in Hematopoietic Stem Cell Transplantation Donors: a Randomized Double Blind Placebo-controlled Trial

Conditions
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Varicella Zoster Infection

Intervention / Treatment
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* Biological: Zostavax
* Biological: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ID varicella zoster vaccine (VZVv) group<br>intradermal 0.65 mL Zostavax | Biological: Zostavax<br>* varicella zoster vaccine<br>|
| Active Comparator: SC VZVv group<br>subcutaneous 0.65 mL Zostavax | Biological: Zostavax<br>* varicella zoster vaccine<br>|
| Placebo Comparator: ID NS Group<br>intradermal 0.65 mL normal saline | Biological: Normal Saline<br>* normal saline placebo vaccine<br>|
| Placebo Comparator: SC NS Group<br>subcutaneous 0.65 mL normal saline | Biological: Normal Saline<br>* normal saline placebo vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Herpes Zoster Reactivation | Incidence of herpes zoster in stem-cell transplant recipients | 12 months post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological response in recipients | Geometric mean concentration of anti-VZV antibody (IU/mL) | 30, 90, 180 and 360 days post transplantation | 
| Immunological response in donors | Geometric mean concentration of anti-VZV antibody (IU/mL) | 30, 90, 180 and 360 days post transplantation | 
| Adverse reaction | Rate of adverse reaction in donors after vaccination | 21 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double-blind, randomized, intradermal, VZVv, HSCT