Persistence of Protection by Shingrix

Study Overview
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Brief Summary
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The study plans to learn more about how the shingles vaccine, Shingrix (SRX), successfully prevents shingles in older people. Two vaccines are currently approved by the Food and Drug Administration (FDA) to prevent shingles. Zostavax is a live virus vaccine which has been available since 2006 and prevents shingles about 50% of the time, though it is less effective the older a person is when they receive it. Shingrix, which was approved by the FDA in 2017, is not a live virus, but has an additive in the vaccine to boost immune response. It is about 97% effective at preventing shingles regardless of a person's age and so far has been effective for at least 4 years after vaccination. Because Zostavax has live virus in it, giving a challenge dose of Zostavax - vOka varicella zoster virus - to people who have received both vaccines (Zostavax or Shingrix) in the past, will allow researchers to learn more about how the body works to prevent shingles and how any shingles vaccination helps protect against shingles.

Official Title
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Persistence of Protection Conferred by Shingrix Against Herpes Zoster

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Zostavax
* Biological: Shingrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-85 General good health Women of non-childbearing potential must be postmenopausal or have undergone hysterectomy or bilateral oophorectomy ARM 1 ONLY: Documented evidence of immunization with ZVL or SRX at least 5 years previously ARM 2 ONLY; Documented evidence of immunization with ZVL 6-12 months prior to enrollment ARM 3 ONLY: Have never received any shingles vaccination Exclusion Criteria: Prior history of herpes zoster (HZ) Blood products received in the 3 months prior to study enrollment or planned for the subsequent week for Arm 1; Arm 2 requires same exclusion; Arm 3 extends the exclusion to the week after the vOka challenge, which is 6 months after completing SRX administration. Significant immune suppressive illness or therapy Concomitant vaccine received within 2 (inactive) or 4 (live) weeks prior to the study or during the first week of the study. Women of childbearing potential. Pregnancy or breastfeeding. Participation in a concurrent clinical study in which the subject will be exposed to and investigational product during the period starting 7 days before the first dose of study vaccine through the completion of the study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ZVL >5 years previously<br>Participants have received Zostavax (ZVL) at least 5 years previously. Will be administered intradermal vOka varicella zoster virus (ZVL) in non-dominant deltoid. A skin biopsy will be performed at the injection site on 20 subjects. | Biological: Zostavax<br>* Intradermal injection of Zostavax<br>|
| Active Comparator: ZVL 6-12 months previously<br>Participants who received ZVL 6-12 months previously will be administered an intradermal dose of vOka varicella zoster virus (ZVL) in non-dominant deltoid. | Biological: Zostavax<br>* Intradermal injection of Zostavax<br>|
| Active Comparator: No previous ZVL<br>Participants who've never received a shingles vaccine will be given the 2 standard doses of RZV. Six months later they will be given the intradermal dose of vOka varicella zoster virus (ZVL) in the non-dominant deltoid. | Biological: Zostavax<br>* Intradermal injection of Zostavax<br>Biological: Shingrix<br>* Given to subjects in Arm 4 who've never had a herpes zoster vaccine<br>|
| Active Comparator: SRX >5 years previously<br>Participants have received Shingrix at least 5 years previously. Will be administered intradermal vOka varicella zoster virus (ZVL) in non-dominant deltoid. A skin biopsy will be performed at the injection site on 20 subjects. | Biological: Zostavax<br>* Intradermal injection of Zostavax<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of Varicella-Zoster Virus (VZV) DNAemia | Varicella-Zoster Virus (VZV) DNAemia will be measured by polymerase chain reaction (PCR) as a surrogate for viremia over the first 7 days after vOka intradermal (ID) challenge. The outcome measure will be the area under the concentration time curve of the VZV DNAemia expressed in DNA copies/ml of blood. | Until VZV DNA is undetectable in the blood, measured up to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunology