Study Description

Herpes zoster (HZ), also known as "shingles", is caused by reactivation and multiplication of the ubiquitous varicella zoster virus (VZV) that remains latent in everyone's sensory neurons following varicella, or "chickenpox". Among individuals who live to age 85, the lifetime risk for HZ is 50%, and more than one in five individuals affected by zoster develop post-herpetic neuralgia, resulting in chronic pain. Other serious complications include encephalitis, permanent vision loss, or more rarely, dissemination and death. Fortunately, a live attenuated vaccine is available and can reduce HZ risk by up to 70%. For patients with rheumatoid arthritis (RA), this vaccine has great potential to provide improved quality of life by reducing the incidence and complications associated with zoster. Due to the underlying disease and/or treatments (e.g. steroids) for rheumatoid arthritis (RA), the risk of herpes zoster in RA patients is approximately double in the general population. This increased risk should make prevention of zoster and vaccination exceedingly important for RA patients.

In light of 1) a substantial elevated HZ risk among RA patients; 2) national data showing most RA patients are not vaccinated for HZ; and 3) the high effectiveness of this vaccine in the general population, the investigators propose to conduct the Varicella zostER VaccinE (VERVE) trial, a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and long-term effectiveness of the live herpes zoster vaccine.  Additionally, the investigators will study vaccine tolerability and long-term effectiveness through a linkage to health plan data to allow for cost-effective follow-up while minimizing participant and study-site burden. Results from this study will facilitate the parent trial and change RA management by demonstrating the clinical safety and immunogenicity of the live zoster vaccine among current anti-TNF users. Rheumatologists and other providers will be able to improve the care, outcomes, and quality of life for patients using anti-TNF therapy, substantially decreasing the morbidity of herpes zoster and its complications over a lifetime.

ELIGIBILITY CRITERIA:

Ages Eligible for Study:           50 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

Inclusion Criteria:

• Must be 50 years of age or older
• Must be currently treated with an anti-TNF therapy** at the time of study drug administration, allowing for small deviations in dosing frequency and logistic feasibility (e.g. study visits to occur on a week day). Date of previous dose of medication is required. Specifically, meets one of the following: Etanercept dose within 9 days (1 week + 2 days), Adalimumab dose within 16 days (2 weeks + 2 days), Certolizumab Subcutaneous (SC) dose within 16 to 32 days depending on frequency schedule (2 weeks + 2 days, or 4 weeks and 4 days), Golimumab Subcutaneous (SC) dose within 32 days (4 weeks + 4 days), Golimumab Intravenous (IV) dose within 64 days (9 weeks + 1 day), Infliximab IV dose within last 64 days (9 weeks + 1 day)

**any form of biosimilar for the above listed anti-TNF medications is acceptable

• Diagnosis of RA or another inflammatory arthritis (Phase Ia); or RA, another inflammatory arthritis, or other inflammatory condition (e.g. psoriasis) requiring use of anti-TNF therapy (Phase Ib and II)
• Phase I subjects must test positive for VZV immunoglobulin G (IgG)
• Subjects should have a self-reported history of prior varicella infection (i.e. chicken pox) or long-term residence (>30 years) in the continental US.
• Phase Ia subjects must not have received any oral or systemic glucocorticoids within 30 days prior to vaccination. Intra-articular glucocorticoid injections and inhaled glucocorticoids within the previous 30 days are acceptable.
• Subjects should be on stable doses of all biologic and non-biologic DMARDs for a minimum of 30 days prior to vaccination.
• Eligible women must be post-menopausal (> 1 year since last menstrual period) or have a surgical history of bilateral oophorectomy or hysterectomy.
• Subjects should be ambulatory, community dwelling and capable of giving informed consent.

Exclusion Criteria:

• Documented VZV negative result
• Prior use of the zoster vaccine (Zostavax®, Merck)
• Glucocorticoids at a prednisone-equivalent daily dose > 10mg/day (for Phase 1b and Phase II participants; all systemic glucocorticoid use is prohibited for Phase Ia patients)
• Any known contraindication to Zostavax® vaccine, including allergy or sensitivity to gelatin or any other vaccine component
• Known HIV/AIDS
• Currently receiving radiation or chemotherapy for any type of malignancy
• Any current use (within the last 30 days) of acyclovir, valacyclovir, famciclovir, or foscarnet
• Receipt of any other immunizations within one month before study vaccination (2 weeks in the case of inactivated influenza vaccines or other non-replicating immunization products [e.g., diphtheria-tetanus (dT), pneumococcal vaccine, hepatitis A vaccine, hepatitis B vaccine]), or scheduled within 6 weeks after recruitment.
• Active infection or inter-current illness (e.g., urinary tract infection, influenza)
• Participated in an investigational study within 1 month prior to study entry
• Active drug or alcohol use, dependence, or any other reason that, in the opinion of the site investigator, would interfere with the study
• Significant underlying illness that would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 3 years)
• Any other reason that, in the opinion of the site investigator, would interfere with required study related evaluations (e.g. uncontrolled comorbidity, life expectancy < 1 year)
• Patients who have household contact with varicella-susceptible pregnant women or severely immunosuppressed individuals without history of primary varicella.

Study Design:

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Prevention

Study Location(s):

Rheumatology Associates, Birmingham, Alabama, United States, 35205

Total Skin and Beauty Dermatology Center, PC, Birmingham, Alabama, United States, 35205

University of Alabama at Birmingham, Birmingham, Alabama, United States, 35294

Rheumatology Associates of North Alabama, PC, Huntsville, Alabama, United States, 35801

Clinical and Translational Research Center of Alabama, PC, Tuscaloosa, Alabama, United States, 35406

SunValley Arthritis Center, Ltd, Peoria, Arizona, United States, 85381

Arthritis Association of Southern California, Los Angeles, California, United States, 90015

The Regents of the University of California Los Angeles, Los Angeles, California, United States, 90095

Rheumatology Consultants of Delaware dba Delaware Arthritis, Lewes, Delaware, United States, 19958

Center for Arthritis and Rheumatic Diseases, Miami, Florida, United States, 33157

Coral Research Clinic Corp, Miami, Florida, United States, 33175

Arthritis Research of Florida, Inc, Palm Harbor, Florida, United States, 34684

Sarasota Arthritis Research Center, Sarasota, Florida, United States, 34239

West Broward Rheumatology Associates, Inc, Tamarac, Florida, United States, 33321

North Georgia Rheumatology Group, Lawrenceville, Georgia, United States, 30046

Arthritis Research Center Foundation, NDB, Wichita, Kansas, United States, 67214

Ochsner Clinic Baton Rouge, Baton Rouge, Louisiana, United States, 70809

Ochsner Clinic Foundation, New Orleans, Louisiana, United States, 70121

Rheumatology & Osteoporosis Specialists, Shreveport, Louisiana, United States, 71101

Boston Medical Center, Boston, Massachusetts, United States, 02118

Pine Hollow Partners, East Lansing, Michigan, United States, 48823

St. Paul Rheumatology, Eagan, Minnesota, United States, 55121

University of Nebraska Medical Center, Omaha, Nebraska, United States, 68106

The Center for Rheumatology, LLP, Albany, New York, United States, 12293

Mary Imogene Bassett Hospital, Bassett Research Institute, Cooperstown, New York, United States, 13326

The Ohio State University, Columbus, Ohio, United States, 43203

Oregon Health & Science University, Portland, Oregon, United States, 97239

Altoona Center for Clinical Research, Duncansville, Pennsylvania, United States, 16635

Carolina Health Specialists, Myrtle Beach, South Carolina, United States, 29572

Arthritis Associates, PLLC, Hixson, Tennessee, United States, 37343

West Tennessee Research Institute, Jackson, Tennessee, United States, 38305

Southwest Rheumatology Research, LLC, Mesquite, Texas, United States, 75150

University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States, 78229

West Virginia Research Institute, PLLC, South Charleston, West Virginia, United States, 25309

Study Website:

https://clinicaltrials.gov/ct2/show/NCT02538341?term=NCT01967316&rank=1