VZV Vaccine for Hematopoietic Stem Cell Transplantation

Varicella Zoster Infection Clinical Trial

— VZIDST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02329457
• Other study ID #: HKU 11-174
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 2014
• Est. completion date: October 2019

Study information

• Verified date: October 2019
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: October 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Chickenpox
• Herpes Zoster
• Varicella Zoster Infection
• Varicella Zoster Virus Infection

Intervention

Biological:
• Zostavax
varicella zoster vaccine
• Normal Saline
normal saline placebo vaccine

Locations

Country	Name	City	State
Hong Kong	Ivan Hung	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (2)

Hata A, Asanuma H, Rinki M, Sharp M, Wong RM, Blume K, Arvin AM. Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants. N Engl J Med. 2002 Jul 4;347(1):26-34. — View Citation

Leung AY, Chow HC, Kwok JS, Lui CK, Cheng VC, Yuen KY, Lie AK, Liang R. Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007 Jun;39(11):661-5. Epub — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Herpes Zoster Reactivation	Incidence of herpes zoster in stem-cell transplant recipients	12 months post transplantation
Secondary	Immunological response in recipients	Geometric mean concentration of anti-VZV antibody (IU/mL)	30, 90, 180 and 360 days post transplantation
Secondary	Immunological response in donors	Geometric mean concentration of anti-VZV antibody (IU/mL)	30, 90, 180 and 360 days post transplantation
Secondary	Adverse reaction	Rate of adverse reaction in donors after vaccination	21 days after vaccination