Clinical trial NCT05775718: Shingrix in Recipients of Allogeneic Transplants
Official title: Safety and Immunogenicity of Shingrix Administered to Recipients of Allogeneic Peripheral and Cord Blood Stem Cell Transplants: Effect of Timing of Vaccination After Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bone Marrow Transplant
Stem Cell Transplant
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2023-03-20
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research is designed to determine if the adjuvanted recombinant glycoprotein E (gE) herpes zoster (HZ) vaccine (Shingrix) has acceptable immunogenicity and safety in people who have undergone allogeneic stem cell transplant (allo-SCT). Specifically, it will determine the effect of the interval after transplantation on the immune response and if an additional dose of vaccine is needed to improve the vaccine-induced responses.

Detailed description: This is a phase II, single center, prospective, unblinded, immunogenicity and safety study. It is anticipated that enrollment will take approximately 6 months. Duration of participation for study subjects is approximately 1 year. During this interval, participants will continue to receive clinical care from the BMT center, which will ensure retention.

Participants will be recruited at their routine clinic visits, which take place every 6 months post-transplantation, or will be recruited by phone. Participants will be consented by study personnel in coordination with the BMT health care providers and subsequently followed in Dr. Levin's Vaccine Research Clinic, where they will also receive the 3rd dose of vaccine.

Eligibility criteria: Inclusion Criteria:

* Allo-SCT recipients being age 18 - 79 years at time of allo-SCT.
* Written informed consent being obtained from the subject
* Two doses of RZV, separated by 2 to 6 months, administered at least 1 year after allo-SCT.
* Enrollment at \>/= 18 months after second dose of Shingrix.
* Female subjects of childbearing potential (FOCBP) enrolled in the study only if they:

  * have practiced adequate contraception for 30 days prior to vaccination with any dose of zoster vaccine and
  * have a negative pregnancy test on the day of each dose of zoster vaccine and
  * agree to continue adequate contraception during the vaccination period and for 2 months after receipt of the vaccine.
* Investigator belief that the participant will comply with the requirements of the protocol

Exclusion Criteria:

* Active Graft Versus Host Disease (aGVHD) at the time of enrollment and receipt of the third dose of RZV
* Having received ≥20 mg prednisone for more than 2 weeks (or equivalent) in the 8 weeks preceding enrollment.
* Receiving any significant immunosuppressive therapy other than for graft maintenance, in the opinion of the investigator.
* Having received a live attenuated vaccine within the last 4 weeks, or inactivated vaccine in the last 2 weeks, prior to enrollment.
* Having a history of HZ after the administration of the primary 2-dose RZV immunization regimen.
* Pregnancy or breastfeeding
* Receiving investigational drugs from 30 day before enrollment or planned during the study
* Inability of participants unable to comply with the study schedule in the opinion of the investigator

Primary outcomes:
measure: Compare the immune response via blood draw of Cohort 1 prior to enrollment to ≥1 year post-transplant
timeFrame: 1 Year
measure: Compare the immune response via blood draw of Cohort 1 prior to enrollment to ≥1 year post-transplant to immune-competent older recipients
timeFrame: 1 Year
measure: Determine adverse events after a 3rd dose of Shingrix administered 18-30 months after primary immunization for Cohort 1
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 1 recipients at 30-60 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 1 recipients at 365 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare the immune response via blood draw of Cohort 2 prior to enrollment to ≥1 year post-transplant
timeFrame: 1 Year
measure: Compare the immune response via blood draw of Cohort 2 prior to enrollment to ≥1 year post-transplant to immune-competent older recipients
timeFrame: 1 Year
measure: Determine adverse events after a 3rd dose of Shingrix administered 18-30 months after primary immunization for Cohort 2
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 2 recipients at 30-60 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 2 recipients at 365 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare the immune response via blood draw of Cohort 3 prior to enrollment to ≥1 year post-transplant
timeFrame: 1 Year
measure: Compare the immune response via blood draw of Cohort 3 prior to enrollment to ≥1 year post-transplant to immune-competent older recipients
timeFrame: 1 Year
measure: Determine adverse events after a 3rd dose of Shingrix administered 18-30 months after primary immunization for Cohort 3
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 3 recipients at 30-60 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw in Cohort 3 recipients at 365 days after the 3rd dose of Shingrix with responses before the administration of the 3rd dose
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw at 30-60 days after a 3rd dose of Shingrix in allo-SCT with responses of immune-competent older adults at the same time point after the dose of Shingrix
timeFrame: 1 Year
measure: Compare gE-specific CMI via blood draw at 365 days after a 3rd dose of Shingrix in allo-SCT with responses of immune-competent older adults at the same time points after the 2nd dose of Shingrix
timeFrame: 1 Year
Secondary outcomes:
measure: Compare gE-specific antibody responses via blood draw in allo-SCT recipients 18-30 months after primary immunization with Shingrix with responses of older immune-competent adults at 1-2 months after the administration of the primary 2-dose regimen
timeFrame: 1 Year
measure: Compare gE-specific antibody responses via blood draw in allo-SCT recipients 18-30 months after primary immunization with Shingrix with responses of immune-competent adults at 1 year after the administration of the primary 2-dose regimen
timeFrame: 1 Year
measure: Compare VZV-specific IL2 responses via blood draw in allo-SCT recipients 18-30 months after primary immunization with Shingrix with responses of older immune-competent adults at 1-2 months after administration of the primary 2-dose regimen
timeFrame: 1 Year
measure: Compare VZV-specific IL2 responses via blood draw in allo-SCT primary immunization 1-2 months after 3rd dose of Shingrix with responses of older immune-competent adults at 1-2 months after administration of primary 2-dose response.
timeFrame: 1 Year
measure: Compare VZV-specific IL2 responses via blood draw in allo-SCT recipients 1 year after the 3rd dose of Shingrix with responses of older immune-competent adults at 1 year after administration of the primary 2-dose regimen.
timeFrame: 1 Year
measure: Compare the gE-specific T cell differentiation via blood draw in allo-SCT recipients before the 3rd dose of Shingrix to imune-competent adults
timeFrame: 1 Year
measure: Compare the gE-specific T cell differentiation via blood draw in allo-SCT recipients after the 3rd dose of Shingrix to immune-competent adults
timeFrame: 1 Year
measure: Compare the gE-specific trained immunity profiles via blood draw in allo-SCT recipients before the 3rd dose of Shingrix with the profile of immune-competent adults
timeFrame: 1 year
measure: Compare the gE-specific trained immunity profiles via blood draw in allo-SCT recipients after the 3rd dose of Shingrix with the profiles of immune-competent adults
timeFrame: 1 year
measure: Determine the incidence of HZ in allo-SCT recipients who received 3 doses of Shingrix.
timeFrame: 1 year
measure: Determine the severity of HZ via blood draw and patient dairy in allo-SCT recipients who received 3 doses of Shingrix.
timeFrame: 1 year
measure: Determine the predictive value of TTV titer via blood draw on the immunogenicity of the 3rd dose of Shingrix in allo-SCT
timeFrame: 1 year
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Myron Levin, MD
role: PRINCIPAL_INVESTIGATOR
References: