Safety and Immunogenicity of Recombinant Zoster Vaccine for Kidney Transplant Recipients

Immunosuppression Clinical Trial

— SIR ZOSTER  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06262776
• Other study ID #: SIRZOSTER1.01
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 2024
• Est. completion date: November 2026

Study information

• Verified date: February 2024
• Source: Central Adelaide Local Health Network Incorporated
• Contact: Matthew J Tunbridge, FRACP
• Phone: 70740000
• Email: Matthew.Tunbridge[@]sa.gov.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: November 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Herpes Zoster
• Immunosuppression
• Vaccine Response Impaired

Intervention

Biological:
• Recombinant zoster vaccine adjuvanted (SHINGRIX)
2 doses of 0.5mL recombinant zoster vaccine adjuvanted intramuscular injection at week 0 and week 8.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Central Adelaide Local Health Network Incorporated	National Health and Medical Research Council, Australia, Royal Prince Alfred Hospital, Sydney, Australia, University of Adelaide

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of shingles	Incidence of shingles in the study cohort from 3 weeks post-vaccination to 12 month follow-up	12 months
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	Concentration of post-vaccination circulating cytokines	Post-vaccination circulating cytokines compared to baseline	3 weeks following second vaccine dose
Secondary	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
Secondary	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
Secondary	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