Systems Biology of Zoster Vaccine

• ClinicalTrials.gov Identifier: NCT04047979
• Recruitment Status: Recruiting
• First Posted: August 7, 2019
• Last Update Posted: December 23, 2022
• Sponsor: Emory University
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Nadine Rouphael, Emory University

Study Description

Brief Summary:

The purpose of the study is to better understand how the immune system responds to the new herpes zoster (shingles) vaccine (Shingrix®). The study will be looking at certain markers in the blood after vaccination with Shingrix®.

Condition or disease	Intervention/treatment	Phase
Zoster; Zoster Varicella; Shingles; Chicken Pox	Biological: Shingrix®	Phase 2

Detailed Description:

Varicella zoster virus (VZV) can cause two distinct diseases: chicken pox (varicella) and herpes zoster (shingles). The primary infection with VZV causes chicken pox, a widespread rash occurring with fever, mostly in childhood. The virus can then remain dormant in a person's body and has the ability to reactivate later in life causing shingles. Shingles is a painful rash, occurring mostly in older individuals or those who have a weakened immune system. After resolution of the rash, individuals may experience persistent pain in the same area, called post-herpetic neuralgia.

The purpose of the study is to better understand how the immune system responds to the new herpes zoster (shingles) vaccine (Shingrix®). In particular, looking at certain markers in the blood after vaccination with Shingrix®.

The study will be an open label randomized clinical trial in healthy older adults. There will be two groups of participants: those aged 50 to 60 years or those who are 70 years old and above, both groups will receive the vaccine. This will help compare the immune response to the herpes zoster vaccine in different age cohorts of older adults.

Subjects will be recruited by flyer advertisements. Interested individuals will be screened for the study and if they qualify they will be consented and enrolled in the study. Blood samples will be collected and banked. There are optional storage of data/specimens for future research including: being contacted for future studies, having contact information and limited medical information entered into a clinic database, and storage of Protected Health Information and samples for future research (yes, no, and de-identified)

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single center, open label mechanistic study in which older adult subjects will receive Zoster vaccine recombinant, adjuvanted Vaccination will occur on Day 0 and Day 60. There will be no randomization, study participant or clinical study personnel blinding, or masking.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: SHINGRIX-Systems Biology of Zoster Vaccine Recombinant, Adjuvanted
• Actual Study Start Date: November 14, 2019
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Younger Group; Participants between the ages of 50 to 60 years will receive two doses of Zoster vaccine recombinant, adjuvanted (Shingrix®)	Biological: Shingrix®; A zoster vaccine recombinant, adjuvanted, recently approved by the FDA for prevention of herpes zoster (shingles) in adults aged 50 years and older. It is given in two doses (0.5 mL each): at 0 and 2 to 6 months.
Experimental: Older Group; Participants who are ≥70 year old will receive two doses of Zoster vaccine recombinant, adjuvanted (Shingrix®)	Biological: Shingrix®; A zoster vaccine recombinant, adjuvanted, recently approved by the FDA for prevention of herpes zoster (shingles) in adults aged 50 years and older. It is given in two doses (0.5 mL each): at 0 and 2 to 6 months.

Outcome Measures

Primary Outcome Measures :

1. Change in innate immune signatures [ Time Frame: Baseline, Days 1, 7, 60, 61, 67 ]
   Will be assessed between D0, D1, and D7 and each dose of Zoster vaccine recombinant, adjuvanted, in both age cohorts: 50-60 years and >70 years of age

Secondary Outcome Measures :

1. Change in safety of Zoster vaccine recombinant, adjuvanted [ Time Frame: Day 180 ]
   Differences in related adverse events and serious adverse events between each dose of Zoster vaccine recombinant, adjuvanted, in both age cohorts.

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Subject must be able to understand and provide informed consent.
2. Adults aged 50-60 years, or community dwelling adults aged 70 years and above.

Exclusion Criteria:

1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol.

2. Receipt of immune products:

   • Receipt of blood products within 6 months prior of the first dose of the study Zoster vaccine or expected receipt through 6 months after vaccination with the second dose of the study Zoster vaccine.
   • Receipt of any vaccine within 4 weeks prior to vaccination with any of the two doses of the study Zoster vaccine or expected receipt within 4 weeks after vaccination with any of the two doses of the study Zoster vaccine.
   • Receipt of any Zoster or varicella vaccines at any time prior to study entry.
3. Subject taking any non-topical antiviral therapy with activity against herpes viruses, including but not limited to acyclovir, famciclovir, valacyclovir, and ganciclovir 3 days prior to each vaccination or 14 days after.
4. Prior history of shingles.

5. Presence of certain co morbidities or immunosuppressive states such as:

   • Chronic medical problems including (but not limited to) insulin-dependent diabetes, severe (at the discretion of the investigator or study physician) heart, lung, liver, or kidney diseases; auto immune diseases; severe gastrointestinal diseases; and uncontrolled hypertension.
   • Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C, tuberculosis, organ transplant, cancer, current and or expected receipt of chemotherapy, radiation therapy, steroids [i.e., > 20 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 90 days); (nasal (less than 1mg/day of fluticasone equivalent inhaled corticosteroid is allowable) and topical steroids are allowed)], antitumor necrosis factor agents, or any other immunosuppressive therapy, anatomic or functional asplenia, congenital immunodeficiency.

6. Conditions that could affect the safety of the subjects such as:

   • Severe reactions to prior vaccinations.
   • History of anaphylactic/anaphylactoid reaction to any component of the vaccines.
   • History of bleeding disorders.
7. Any acute illness, including any fever (> 100.4 F [> 38.0 C], regardless of the route) within 3 days prior to study entry.
8. Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.
9. Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data.
10. Use of investigational drugs within 12 months of participation.
11. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator or study physician, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
12. Women of childbearing potential.

Contacts and Locations

Contacts

Contact: Nadine Rouphael, MD; 404-712-1435; nroupha@emory.edu

Locations

United States, Georgia

The Hope Clinic; Recruiting

Decatur, Georgia, United States, 30030

Contact: Nadine Rouphael, MD 404-712-1435 nroupha@emory.edu

Sponsors and Collaborators

Emory University

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Nadine Rouphael, MD; Emory University

More Information

• Responsible Party: Nadine Rouphael, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT04047979
• Other Study ID Numbers: IRB00105838; 1U19AI090023 ( U.S. NIH Grant/Contract )
• First Posted: August 7, 2019
• Last Update Posted: December 23, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All of the individual participant data collected during the trial, after deidentification.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: At the time of publication or 9 months after submission of the manuscript. It will be available indefinitely.

Access Criteria

Data will be uploaded into www.immport.org and made available to researchers with a registered account.

Type of Analysis: Any Purpose

Mode of Access: Data will be shared on www.immport.org

• URL: http://www.immport.org

• 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

Keywords provided by Nadine Rouphael, Emory University:

Zoster; Immune responses; Vaccine; Vaccine Trials; Clinical Trials; Chicken Pox; Shingles

Additional relevant MeSH terms:

Herpes Zoster; Chickenpox; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections