The Immunogenicity and Safety of Zostavax® and Shingrix® in Rheumatoid Arthritis Patients Using Abatacept

NCT03604406 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 10433
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 5

Brief Summary

This investigator-initiated study will serve as a sub-study for the American College of Rheumatology-sponsored VERVE protocol currently funded by the NIH. This double-blinded multicenter randomized pragmatic trial is designed to determine whether Zostavax or Shingrix are safe and effective in patients with rheumatoid arthritis (RA) currently using anti-tumor necrosis factor (TNF) therapies. Inclusion/exclusion criteria for this sub-study mirror that of the parent VERVE trial with the exception of abatacept therapy being allowed. Preliminary data from the VERVE parent protocol enrolling patients using anti-TNF therapy is encouraging in that few patients experienced adverse events (56 adverse events in 50 participants, out of 140 participants in total) and that 96.2% of these adverse events were considered either mild or moderate. Importantly, there have been no instances of vaccine dissemination or zoster events to date.

Conditions

Herpes Zoster; Inflammatory Disease; Rheumatoid Arthritis

Keywords

Shingles; abatacept; Varicella Zoster Vaccine

Outcome Measures

Primary Outcomes (2)

• Change in ELISPOT response from baseline to week 6, and one year post vaccination

  Surrogate measures of vaccine efficacy will be performed on all patients using samples collected at baseline prior to vaccination, and subsequently at 6 weeks, and one year post vaccination. These measures will include: a. Frequency of VZV-specific T cells as measured by interferon-gamma ELISPOT assay. Changes in these outcome measures will be evaluated using geometric means and percentage increases in geometric means of (a) VZV-specific reactive lymphocytes.

  1) Baseline visit prior to vaccination; 2) 6 weeks post-vaccination; 3) 1 year post-vaccination

• Change in IgG titer from baseline to week 6, and one year post vaccination

  Surrogate measures of vaccine efficacy will be performed on all patients using samples collected at baseline prior to vaccination, and subsequently at 6 weeks, and one year post vaccination. These measures will include: b. VZVgp-specific IgG titer as measured by ELISA Changes in these outcome measures will be evaluated using geometric means and percentage increases in geometric means of (b) VZV antibody titers in vaccine recipients as compared to placebo, as well as relative to baseline measures prior to vaccination.

  1) Baseline visit prior to vaccination; 2) 6 weeks post-vaccination; 3) 1 year post-vaccination

Secondary Outcomes (1)

• Development of Varicella Zoster Virus

  Within 42 days of vaccination

Study Arms (4)

Varicella Zoster Vaccine (Zostavax)

EXPERIMENTAL

Live zoster vaccine injection will be administered as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Biological: Varicella Zoster Vaccine

Placebo Injection (Zostavax Comparator)

PLACEBO COMPARATOR

Saline injection will be administered as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Other: Placebo Injection

Varicella Zoster Vaccine (Shingrix)

EXPERIMENTAL

Non-live zoster vaccine injection will be administered twice, 8 weeks apart, as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Biological: Varicella Zoster Vaccine

Placebo Injection (Shingrix Comparator)

PLACEBO COMPARATOR

Saline injection will be administered twice, 8 weeks apart, as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Other: Placebo Injection

Interventions

Varicella Zoster Vaccine BIOLOGICAL

live-attenuated vaccine to prevent herpes zoster

Also known as: Zostavax

Varicella Zoster Vaccine (Zostavax)

Placebo Injection OTHER

Saline solution injection

Placebo Injection (Shingrix Comparator); Placebo Injection (Zostavax Comparator)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• be \>= 50 years of age or older (for the Zostavax® sub-study only)
• be \>= 18 years of age or older (for the Shingrix® sub-study only)
• be currently treated with abatacept therapy at the time of enrollment
• Eligible women must be post-menopausal (\> 1 year since last menstrual period) or have a surgical history of bilateral oophorectomy or hysterectomy (for the Zostavax® sub-study only).
• Female participants of childbearing potential may be enrolled in the study if the participant (for the Shingrix® sub-study only):
• Has practiced adequate contraception for 30 days prior to vaccination; and
• Has a negative urine pregnancy test on the day of the first vaccination; and
• Has agreed to continue adequate contraception during the primary treatment period and for 2 months after completion of the vaccination series (Week 16)
• Patients must have a history of prior chicken pox (for the Zostavax® sub-study only; for patients who do not recall prior chicken pox, a positive varicella IgG serology can be used to document prior exposure)

You may not qualify if:

• prior Zostavax® receipt (for the Zostavax® sub-study only; the Shingrix® sub-study will allow prior Zostavax® receipt if 6 months or greater prior to enrollment)
• active contraindications to vaccination including allergy or sensitivity to gelatin or any other vaccine component
• acute illness or infection
• HIV/AIDS
• methotrexate use \> 25 mg/week
• dose of DMARDs not stable for \> 30 days
• concomitant TNF antagonist use
• receiving radiation or chemotherapy for cancer treatment
• current leukemia
• lymphoma, or other cancer affecting bone marrow or lymphatic system
• cellular immunodeficiency
• current use (within the last 30 days) of anti-viral medications against the herpesvirus family
• Received any live virus vaccine within 28 days prior to study entry (Zostavax® sub-study only)
• Administration or planned administration of any live vaccine \<28 days before the first study vaccination or through 28 days after the second study vaccination (Shingrix ® sub-study only)
• received any inactivated vaccine within 7 days prior to study entry (Zostavax® sub-study only)

Sponsors & Collaborators

• Kevin Winthrop: lead
• University of Alabama at Birmingham: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (5)

St. Luke's Health System

Boise, Idaho, 83702, United States

Location

St. Paul Rheumatology

Eagan, Minnesota, 55121, United States

Location

Jayashree Sinha, MD

Clovis, New Mexico, 88101, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Arthritis Associates

Hixson, Tennessee, 37343, United States

Location

MeSH Terms

Conditions

Herpes Zoster; Arthritis, Rheumatoid

Interventions

Herpes Zoster Vaccine

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chickenpox Vaccine; Herpesvirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 27, 2018
• Study Start: May 8, 2014
• Primary Completion: June 30, 2024
• Study Completion: January 12, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (5)