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

NCT02538341 | Completed Phase 2 Results DMC

• 1 other identifier: VERVE-UM1
• Study Type: interventional
• Target: 617
• Locations: 1 country
• Sites: 34

Brief Summary

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

Conditions

Rheumatoid Arthritis; Inflammatory Arthritis; Arthritis; Psoriatic Arthritis; Psoriasis; Ankylosing Spondylitis; Enteropathic Arthritis; Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 6 Weeks

  Study protocol defined measure for immunogenicity samples.

  6 weeks post vaccination

• GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 6 Weeks

  Study protocol defined measure for immunogenicity samples.

  6 weeks post vaccination

Secondary Outcomes (5)

• GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Immunoglobulin G (IgG) Levels From Baseline at 1 Year

  Baseline to 1 year

• GMFR (Geometric Mean Fold Rise ) in Varicella Zoster Virus (VZV) Enzyme-linked Immune Absorbent Spot (ELISpot) Interferon Gamma (IFNg) Levels From Baseline at 1 Year

  Baseline to 1 year

• Number of Samples With Confirmed Varicella

  "Placebo Normal Saline Arm/Group was assessed up to 6 months and the "Zoster Vaccine Live (Zostavax)" Arm/Group was assessed up to 1 year

• Vaccine Tolerability Within 42 Days Following Vaccination.

  42 days post vaccination

• Evaluate Rheumatoid Arthritis Disease Activity Using the Clinical Disease Activity Index (CDAI)

  42 days post vaccination

Study Arms (2)

Zostavax (Zoster Vaccine Live)

ACTIVE COMPARATOR

Zostavax (zoster vaccine live) is used to prevent herpes zoster (HZ) virus (shingles) in people age 50 and older. Patients randomized to this arm will receive active herpes zoster (HZ) vaccine. It is administered as a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm.

Biological: Herpes Zoster (HZ) Vaccine

Placebo Normal Saline

PLACEBO COMPARATOR

Saline injection: patients randomized to this arm will receive a single 0.65 mL dose subcutaneously in the deltoid region of the upper arm.

Drug: Placebo

Interventions

Herpes Zoster (HZ) Vaccine BIOLOGICAL

Also known as: Zostavax

Zostavax (Zoster Vaccine Live)

Placebo DRUG

Also known as: Normal Saline

Placebo Normal Saline

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 50 years of age or older
• Must be currently treated with an anti-tumor necrosis factor (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-tumor necrosis factor (TNF) medications is acceptable
• Diagnosis of rheumatoid arthritis or another inflammatory arthritis (Phase 1A); or other inflammatory condition (e.g. psoriasis) requiring use of anti-tumor necrosis factor (TNF) therapy (Phase 1B and II)
• Phase I subjects must test positive for varicella-zoster virus (VZV) antibody 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 United States.
• 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 Disease-modifying antirheumatic drugs (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.

You may not qualify if:

• Documented varicella-zoster virus (VZV) antibody immunoglobulin G (IgG) 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 1A patients)
• Any known contraindication to Zostavax® vaccine, including allergy or sensitivity to gelatin or any other vaccine component
• Known human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Oregon Health and Science University: collaborator

Study Sites (34)

Rheumatology Associates, PC

Birmingham, Alabama, 35205, United States

Location

Total Skin and Beauty Dermatology Center, PC

Birmingham, Alabama, 35205, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Rheumatology Associates of North Alabama, PC

Huntsville, Alabama, 35801, United States

Location

Clinical and Translational Research Center of Alabama, PC

Tuscaloosa, Alabama, 35406, United States

Location

SunValley Arthritis Center, Ltd

Peoria, Arizona, 85381, United States

Location

Arthritis Association of Southern California

Los Angeles, California, 90015, United States

Location

The Regents of the University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Rheumatology Consultants of Delaware dba Delaware Arthritis

Lewes, Delaware, 19958, United States

Location

Center for Arthritis and Rheumatic Diseases

Miami, Florida, 33157, United States

Location

Coral Research Clinic Corp

Miami, Florida, 33175, United States

Location

Arthritis Research of Florida, Inc

Palm Harbor, Florida, 34684, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

West Broward Rheumatology Associates, Inc

Tamarac, Florida, 33321, United States

Location

North Georgia Rheumatology Group

Lawrenceville, Georgia, 30046, United States

Location

Arthritis Research Center Foundation, NDB

Wichita, Kansas, 67214, United States

Location

Ochsner Clinic Baton Rouge

Baton Rouge, Louisiana, 70809, United States

Location

Ochsner Clinic Foundation, New Orleans

New Orleans, Louisiana, 70121, United States

Location

Rheumatology & Osteoporosis Specialists

Shreveport, Louisiana, 71101, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Pine Hollow Partners

East Lansing, Michigan, 48823, United States

Location

St. Paul Rheumatology

Eagan, Minnesota, 55121, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68106, United States

Location

The Center for Rheumatology, LLP

Albany, New York, 12293, United States

Location

Mary Imogene Bassett Hospital, Bassett Research Institute

Cooperstown, New York, 13326, United States

Location

The Ohio State University

Columbus, Ohio, 43203, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Carolina Health Specialists

Myrtle Beach, South Carolina, 29572, United States

Location

Arthritis Associates, PLLC

Hixson, Tennessee, 37343, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Southwest Rheumatology Research, LLC

Mesquite, Texas, 75150, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

West Virginia Research Institute, PLLC

South Charleston, West Virginia, 25309, United States

Location

Related Publications (1)

• Curtis JR, Cofield SS, Bridges SL Jr, Bassler J, Deodhar A, Ford TL, Huffstutter J, Jankeel A, Kivitz A, Kamal S, Lindsey S, Messaoudi I, Mendoza N, Michaud K, Mikuls TR, Ridley D, Shergy W, Siegel SAR, Winthrop KL. The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial. Ann Intern Med. 2021 Nov;174(11):1510-1518. doi: 10.7326/M20-6928. Epub 2021 Sep 28.

  PMID: 34570596 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis; Arthritis, Psoriatic; Psoriasis; Spondylitis, Ankylosing; Crohn Disease

Interventions

Vaccines; Herpes Zoster Vaccine; Saline Solution

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Skin Diseases, Papulosquamous; Skin Diseases; Axial Spondyloarthritis; Ankylosis; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Chickenpox Vaccine; Herpesvirus Vaccines; Viral Vaccines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Jeffrey R. Curtis
• Organization: University of Alabama at Birmingham

jrcurtis@uabmc.edu

205-975-2176

Study Officials

• Jeffrey R Curtis, MD, MS, MPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: September 2, 2015
• Study Start: May 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: November 23, 2021
• Results First Posted: November 23, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (34)