Shingrix in Renal Transplant Recipients

Study Overview
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Brief Summary
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This study evaluates the safety and immune response of the Shingrix vaccine in kidney transplant recipients. Participants on the waiting list for kidney transplant will be given the standard 2 doses of Shingrix. Those participants who have been transplanted by 16 months, may be given a 3rd dose of Shingrix.

Detailed Description
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Herpes Zoster (HZ) is a common complication of kidney transplant because of the immune suppressive drugs necessary to prepare the recipient for the transplanted organ and to protect it from rejection. The use of the live vaccine, Zostavax, in transplant recipients is contraindicated due to their impaired immune status. This study is being done to determine vaccine responses to the FDA approved shingles vaccine, Shingrix, in patients with chronic renal failure eligible for kidney transplant. Persistence of immune responses after kidney transplantation, and immunologic advantage of a third dose of Shingrix to renal transplant recipients will be assessed. Additionally, safety, tolerability, and occurrence of HZ will be evaluated. 60 participants will be enrolled from the renal transplant services at University of Colorado Anschutz Medical Campus.

Official Title
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Safety and Immunogenicity of Shingrix in Renal Transplant Recipients

Conditions
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Kidney Transplant Recipient Response to Shingrix Vaccine

Intervention / Treatment
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* Biological: Shingrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On the waiting list at the participating institutions for renal transplantation with anticipated transplantation to occur at > 3 months to 16 months after listing. Female subjects of non-childbearing potential (tubal ligation, hysterectomy,ovariectomy or post-menopausal Female subjects of childbearing potential who have practiced adequate contraception for 30 days prior to vaccination, have a negative pregnancy test on day of vaccination, and have agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccine series Exclusion Criteria: Therapy in the pre-transplant period that in the opinion of the investigator is immune suppressive Herpes Zoster in prior 3 years Herpes zoster vaccine or varicella vaccine within 3 years of study entry Any positive cPRA score prior to enrollment Acute illness at the time of vaccination which in the opinion of the investigator will alter immune response Any other active immunosuppressive or immunodeficient condition resulting from disease (e.g. malignancy, HIV, or a medical therapy). Allergy to any of the components of Shingrix No investigational drugs from 30 days before enrollment or planned during the study. No non-live vaccines within the 2 weeks prior to any dose of Shingrix or until 30 days after any dose of Shingrix. No live virus vaccines within 4 weeks prior to any dose of Shingrix or until 30 days after any dose Pregnant or lactating female Multi-organ transplantation Travel time from study site that is more than 2 hours for visit or transport of fresh blood samples

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transplanted subject<br>In addition to receiving standard dose (2) of Shingrix prior to transplantation, participant may receive a 3rd dose several months after transplantation if they meet criteria related to no rejection. | Biological: Shingrix<br>* Both arms receive standard 2 doses of Shingrix. Transplanted subjects may receive 3rd dose.<br>|
| Sham Comparator: Non-Transplanted subject<br>Receives standard Shingrix dose (2), but not transplanted within 16 month time frame post-dose, so does not receive additional Shingrix dose. | Biological: Shingrix<br>* Both arms receive standard 2 doses of Shingrix. Transplanted subjects may receive 3rd dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunology - Glycoprotein E(gE)-specific antibody and cell mediated immunity (CMI) will be measured. | The kinetics and magnitude of antibody and CMI responses will be compared to immunologic data previously determined during studies of immune competent subjects. | 12 months after vaccination | 
| Safety information acquisition - Adverse events (AEs) | Safety and tolerability data about local and systemic adverse events will be collected via vaccine diaries. | Adverse event data collected for 30 days after each vaccine dose. | 
| Ascertaining occurrence of HZ in vaccinees | Subjects will be asked to notify study team and to complete an HZ questionnaire should they develop herpes zoster during the study. | At every contact from enrollment up to Month 36 | 
| Safety information acquisition - Serious Adverse Events (SAEs) and potential immune-mediated diseases (pIMDs) | Subjects will be queried about SAEs and pIMDs at every contact. | SAEs and pIMD data collected from enrollment up to 12 months after Visit 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic vaccine responses in patients with chronic renal failure | gE-Specific IL2 SFC/10; interleukin-2 = IL2, spot forming cells = SFC | 1 month after 2nd dose of Shingrix. |