Safety and Immunogenicity of Recombinant Zoster Vaccine for Kidney Transplant Recipients (SIR ZOSTER)

Safety and Immunogenicity of Recombinant Zoster Vaccine for Kidney Transplant Recipients (SIR ZOSTER)

The goal of this clinical trial is to compare responses to Varicella Zoster vaccination between kidney transplant patients on different medication regimens, and their healthy co-habitants. The main questions it aims to answer are:

1. Are there differences in vaccination immunological responses in kidney transplant patients on different immunosuppression regimens?
2. Are there differences in vaccination immunological responses between kidney transplant patients and their healthy co-habitants? Participants will all receive a 2-dose course of SHINGRIX recombinant Zoster vaccination, and have immunological responses measured and compared at 5 timepoints between 1 week to 1 year post-vaccination.

Study Overview

• Status: Not yet recruiting
• Conditions: Immunosuppression; Vaccine Response Impaired
• Intervention / Treatment: Biological: Recombinant zoster vaccine adjuvanted (SHINGRIX)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthew J Tunbridge, FRACP; Phone Number: 70740000; Email: Matthew.Tunbridge@sa.gov.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Single organ kidney transplant recipient, currently receiving a specific immunosuppression regimen:

  1. Calcineurin inhibitor (tacrolimus or cyclosporine), antimetabolite (mycophenolate derivative or azathioprine), and oral steroid (n = 30)
  2. Calcineurin inhibitor (tacrolimus or cyclosporine), mTOR inhibitor (sirolimus or everolimus), and oral steroid (n = 30)
  3. mTOR inhibitor (sirolimus or everolimus), antimetabolite (mycophenolate derivative or azathioprine), and oral steroid (n = 30)
• Aged >18 years
• estimated glomerular filtration rate (GFR) > 15 mL/min/1.73m2
• Previous documented infection with Varicella zoster (known infection history or positive Varicella zoster IgG result)

OR

• Healthy household cohabitant of kidney transplant recipient enrolled in trial (n = 30)
• Aged > 50 years
• Previous documented infection with Varicella zoster (known infection history or positive Varicella zoster IgG result)

Exclusion Criteria:

• Unable or unwilling to provide informed consent to participate in the trial
• No previous infection with Varicella zoster (chickenpox)
• Known allergy to or intolerance of the contents of the SHINGRIX vaccine
• Current pregnancy
• For healthy household cohabitants, history of primary immunodeficiency, documented vaccine hypo-responsiveness, or active immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination group; All participants will receive the assigned intervention, a 2-dose course of Zoster recombinant adjuvanted vaccine. Study participants will include kidney transplant recipients receiving specific immunosuppressive medications, and non-immunosuppressed household cohabitants, with comparisons made in magnitude of vaccine response.	Biological: Recombinant zoster vaccine adjuvanted (SHINGRIX); 2 doses of 0.5mL recombinant zoster vaccine adjuvanted intramuscular injection at week 0 and week 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional T cell memory	ELISpot measurement of interferon gamma spot-forming units following 18-hour stimulation of peripheral blood mononuclear cells with Zoster gE protein-derived peptide array	3 weeks following second vaccine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of virus specific T cells	Change in frequency of CD8+ Zoster gE protein-specific T cells identified by flow cytometry as CD8+CD134+CD69+ following 24-hour stimulation with a gE protein-derived peptide array	3 weeks and 52 weeks following second vaccine dose
Magnitude of antibody response	Anti Varicella zoster gE Immunoglobulin M (IgM) and IgG antibody titres compared to baseline	3 weeks and 52 weeks following second vaccine dose
Concentration of post-vaccination circulating cytokines	Post-vaccination circulating cytokines compared to baseline	3 weeks following second vaccine dose
Frequency of polyfunctional T cells	Change in frequency of Zoster gE protein-specific polyfunctional T cells identified by flow cytometry intracellular cytokine staining (interferon-gamma, interleukin-2, tumour necrosis factor) following 24-hour stimulation with a gE protein-derived peptide array.	3 weeks and 52 weeks following second vaccine dose
Magnitude of vaccine-induced cross-protective antiviral responses	T cells will be investigated for cross-protective herpesviridae responses using interferon gamma ELISpot compared to baseline following 24-hour stimulation with a gE protein-derived peptide array.	3 weeks and 52 weeks following second vaccine dose
Frequency of virus-specific T stem cell memory compared to baseline	Frequency of Zoster gE protein-specific T stem cell memory (Tscm) will be determined by flow cytometry based on expression of T cell phenotypic markers (CD27+CD45RA+CD95+) on activation-induced marker-positive CD4 and CD8 T cells	3 weeks and 52 weeks following second vaccine dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of shingles	Incidence of shingles in the study cohort from 3 weeks post-vaccination to 12 month follow-up	12 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Safety of two-dose Zoster recombinant vaccine adjuvanted as measured by reported adverse events following immunisation using CTCAE v4.0 1 and 3 weeks after each vaccination, and 12 months after vaccination.	12 months
Tolerability of vaccination regimen as assessed by EQ-5D	Tolerability of two-dose Zoster recombinant vaccine adjuvanted as measured by quality of life questionnaire EuroQol-5 dimensional (EQ-5D) questionnaire at baseline and 3 weeks after second vaccine dose. This questionnaire assesses quality of life rated on a scale of 0 (worst) to 100 (best), and assesses functional capacity rated on a scale of 0 (best) to 5 (worst) across 5 domains: mobility, self-care, usual activities, pain/discomfort, anxiety/depression.	3 weeks following second vaccine dose

Collaborators and Investigators

• Sponsor: Central Adelaide Local Health Network Incorporated
• Collaborators: National Health and Medical Research Council, Australia; University of Adelaide; Royal Prince Alfred Hospital, Sydney, Australia
• Investigators: Principal Investigator: Patrick T Coates, FRACP, Central and Northern Adelaide Renal and Transplantation Services

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: SIRZOSTER1.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Identifiable data will not be publicly released, however, de-identified data will be made available in combination with publication of study results either as supplementary material or on public repository. Study protocol and statistical analysis plan will be made available as supplementary material with publication of results.
• IPD Sharing Time Frame: Data will be made available following publication of trial results, and will be available in perpetuity.
• IPD Sharing Access Criteria: Trial results and supporting information outlined above will be made available through open access publishing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No