Safety and Effectiveness of Live Zoster Vaccine in Anti-Tumor Necrosis Factor (TNF) Users (VERVE Trial)



Status:Active, not recruiting
Conditions:Arthritis, Psoriasis, Psoriasis, Rheumatoid Arthritis, Neurology, Neurology, Gastrointestinal, Crohns Disease
Therapuetic Areas:Dermatology / Plastic Surgery, Gastroenterology, Neurology, Rheumatology
Healthy:No
Age Range:50 - Any
Updated:4/5/2019
Start Date:May 2016
End Date:December 2019

Use our guide to learn which trials are right for you!

Safety and Effectiveness of Live Zoster Vaccine in Anti-TNF Users (VERVE Trial)

The VaricElla zosteR VaccinE (VERVE) trial evaluates the safety and effectiveness of the
herpes zoster (shingles) vaccine, Zostavax, in patients over 50 years old with arthritis and
other diseases who are using anti-TNF therapy and who have not previously received the
vaccine.

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 fact, because of a higher overall absolute risk for zoster in RA, the vaccine
yields a comparable or even greater absolute risk reduction to reduce the risk of shingles
and post-herpetic neuralgia in an RA population as it does in the general population.
However, the use of the zoster vaccine in RA patients is very low (< 5%), and less frequently
used than for the general population.

National guidelines from the Centers for Disease Control's (CDC) Advisory Committee on
Immunization Practices (ACIP) recommend a single dose of the zoster vaccine for all
individuals age 60 or older, with the vaccine more recently gaining FDA-approval for
administration to persons age 50 and older. While a large number of RA patients would
otherwise be recommended to receive this vaccine on the basis of age, theoretical safety
concerns related to vaccination likely explain the very low vaccination rates observed.
Currently, the Federal Drug Administration (FDA), the ACIP, and the American College of
Rheumatology (ACR) consider the live zoster vaccine contraindicated in patients receiving
immunosuppressive medications, such as biologic therapies. Such contraindication stems from
the theoretical safety concern that these individuals could develop a varicella-like
infection from the vaccine virus strain. However, investigators hypothesize that this vaccine
can safely be given in this setting, as no published data is available to suggest that these
safety concerns are warranted. A growing body of observational data suggests that vaccinating
RA patients receiving biologic therapies with this vaccine may in fact be safe. Moreover, and
similarly with little or no evidence, the ACIP considers the vaccine safe and acceptable for
patients using methotrexate at doses commonly used to treat RA (e.g. <= 25mg/week) and for
patients using glucocorticoids at prednisone-equivalent doses of ≤ 20 mg/day.

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. This study will
recruit 1,000 individuals age 50 years or older currently receiving anti-TNF therapy for RA
or other diseases. Within a relevant 6-week safety window, the investigators will collect
serious adverse events (satisfying a regulatory definition of a SAE) including non-serious
events of vaccine-strain varicella-like infection or herpes zoster. Beyond the key public
health importance of the clinical question addressed, clinical trial methodological
innovations anticipated for this unique large pragmatic trial. 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.

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.
We found this trial at
34
sites
Mesquite, Texas 75150
Principal Investigator: Atul K Singhal, MD
?
mi
from
Mesquite, TX
Click here to add this to my saved trials
1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
Principal Investigator: Jeffrey R Curtis, MD, MS, MPH
Phone: 205-934-7727
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Kevin Winthrop, MD
Phone: 503-494-1384
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
?
mi
from
Portland, OR
Click here to add this to my saved trials
4502 Medical Drive
San Antonio, Texas 78284
(210) 567-7000
Principal Investigator: Agustin Escalante, MD
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
?
mi
from
San Antonio, TX
Click here to add this to my saved trials
Albany, New York 12206
Principal Investigator: Joel Kremer, MD
?
mi
from
Albany, NY
Click here to add this to my saved trials
Baton Rouge, Louisiana 70809
Principal Investigator: Stephen Lindsey, MD
?
mi
from
Baton Rouge, LA
Click here to add this to my saved trials
Birmingham, Alabama 35205
Principal Investigator: Henry Townsend, MD
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Birmingham, Alabama 35205
Principal Investigator: James Krell, MD
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Boston, Massachusetts 02118
Principal Investigator: Sharmeel Wasan, MD
?
mi
from
Boston, MA
Click here to add this to my saved trials
281 W. Lane Ave
Columbus, Ohio 43210
(614) 292-6446
Principal Investigator: Ali Ajam, MD
Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Cooperstown, New York 13326
Principal Investigator: Donald Raddatz, MD
?
mi
from
Cooperstown, NY
Click here to add this to my saved trials
Duncansville, Pennsylvania 16635
Principal Investigator: Alan Kivitz, MD
?
mi
from
Duncansville, PA
Click here to add this to my saved trials
Eagan, Minnesota 55121
Principal Investigator: David Ridley, MD
?
mi
from
Eagan, MN
Click here to add this to my saved trials
East Lansing, Michigan 48823
Principal Investigator: Iris Zink, NP
?
mi
from
East Lansing, MI
Click here to add this to my saved trials
Hixson, Tennessee 37343
Principal Investigator: Joseph Huffstutter, MD
?
mi
from
Hixson, TN
Click here to add this to my saved trials
Huntsville, Alabama 35801
Principal Investigator: William Shergy, MD
?
mi
from
Huntsville, AL
Click here to add this to my saved trials
Jackson, Tennessee 38305
Principal Investigator: Jacob Aelion, MD
?
mi
from
Jackson, TN
Click here to add this to my saved trials
Lawrenceville, Georgia 30046
Principal Investigator: Theresa Lawrence-Ford, MD
?
mi
from
Lawrenceville, GA
Click here to add this to my saved trials
Lewes, Delaware 19958
Principal Investigator: Jose Pando, MD
?
mi
from
Lewes, DE
Click here to add this to my saved trials
Los Angeles, California
Principal Investigator: Daniel Furst, MD
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Los Angeles, California 90025
Principal Investigator: Veena Ranganath, MD
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Miami, Florida 33173
Principal Investigator: Michael Weitz, MD
?
mi
from
Miami, FL
Click here to add this to my saved trials
Miami, Florida 33175
Principal Investigator: Edel Abreu, MD
?
mi
from
Miami, FL
Click here to add this to my saved trials
Myrtle Beach, South Carolina 29572
Principal Investigator: Douglas Conaway, MD
?
mi
from
Myrtle Beach, SC
Click here to add this to my saved trials
New Orleans, Louisiana 70121
Principal Investigator: William Davis, MD
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
Emile St
Omaha, Nebraska 68198
(402) 559-4000
Principal Investigator: Ted Mikuls, MD
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
?
mi
from
Omaha, NE
Click here to add this to my saved trials
Palm Harbor, Florida 34684
Principal Investigator: Anthony Sebba, MD
?
mi
from
Palm Harbor, FL
Click here to add this to my saved trials
6818 West Thunderbird Road
Peoria, Arizona 85381
Principal Investigator: Joy Schechtman, MD
?
mi
from
Peoria, AZ
Click here to add this to my saved trials
Sarasota, Florida 34239
Principal Investigator: Jeffrey Kaine
?
mi
from
Sarasota, FL
Click here to add this to my saved trials
820 Jordan Street
Shreveport, Louisiana 71101
Principal Investigator: Aaron Broadwell, MD
?
mi
from
Shreveport, LA
Click here to add this to my saved trials
1740 Union Carbide Drive
South Charleston, West Virginia 25309
Principal Investigator: Suzanne Gharib, MD
?
mi
from
South Charleston, WV
Click here to add this to my saved trials
Tamarac, Florida 33321
Principal Investigator: Steven Kimmel, MD
?
mi
from
Tamarac, FL
Click here to add this to my saved trials
Tuscaloosa, Alabama 35406
Principal Investigator: Richard Jones, MD
?
mi
from
Tuscaloosa, AL
Click here to add this to my saved trials
?
mi
from
Wichita, KS
Click here to add this to my saved trials