Persistence of Protection by Shingrix

Persistence of Protection Conferred by Shingrix Against Herpes Zoster

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.

Study Overview

• Status: Completed
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: Zostavax; Biological: Shingrix

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Trials Center at University of Colorado Anschutz Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ZVL >5 years previously; 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; Intradermal injection of Zostavax
Active Comparator: ZVL 6-12 months previously; 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; Intradermal injection of Zostavax
Active Comparator: No previous ZVL; 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; Intradermal injection of Zostavax; Biological: Shingrix; Given to subjects in Arm 4 who've never had a herpes zoster vaccine
Active Comparator: SRX >5 years previously; 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; Intradermal injection of Zostavax

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Adriana Weinberg, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2020
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: immunology
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: 18-0580; 1U01AI141919-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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