Zostavax in Rheumatoid Arthritis

Study Description

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Brief Summary:

Herpes Zoster (shingles) is caused by reactivation of latent varicella zoster virus (VZV) that usually occurs decades following initial exposure. The risk of developing shingles increases with age. Shingles presents as a painful, itchy blistering rash that usually involves a single portion of the skin and lasts about 7-10 days. The risk of developing shingles increases with age in healthy people, and has been shown in some studies to be increased in people with rheumatoid arthritis and other autoimmune diseases.

Zostavax, a live-attenuated vaccine against the varicella zoster virus, was first approved by the FDA for the prevention of Shingles among people 60 years and older, and is now approved for use in people aged 50 years and older. Because rheumatoid arthritis and some of the medications used to treat rheumatoid arthritis can impair the body's immune system, it is not known how much of an immune response can be generated in people with rheumatoid arthritis.

The goals of this study are to measure the immune response after standard vaccination with Zostavax in people with rheumatoid arthritis in comparison to people with healthy immune systems. All participants will be 50 years old or older, and subjects with rheumatoid arthritis will not be eligible if they are taking certain biologic medications, including TNF inhibitors (Etanercept or Adalimumab). Ten healthy subjects and 10 subjects with rheumatoid arthritis will all receive a single vaccination with Zostavax, then will be followed for 12 weeks to assess the immune response and for the development of local rash or other potential side effects.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis; Varicella Zoster	Drug: Zostavax (varicella zoster virus) vaccine	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Immune Response to Varicella Zoster Vaccination (ZOSTAVAX) in Subjects With Rheumatoid Arthritis
Study Start Date :	January 2012
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	October 2018

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Rheumatoid Arthritis; 10 subjects with mild rheumatoid arthritis aged 50 years and older will be enrolled and will receive a single dose of Zostavax vaccine.	Drug: Zostavax (varicella zoster virus) vaccine; Standard vaccination protocol for Zostavax will be utilized. 0.65 ml (19,400 plaque forming units) Zostavax will be administered subcutaneously once at the baseline visit
Active Comparator: Healthy Subjects; 10 healthy subjects aged 50 years or older who have not been previously immunized, will receive a single injection of Zostavax.	Drug: Zostavax (varicella zoster virus) vaccine; Standard vaccination protocol for Zostavax will be utilized. 0.65 ml (19,400 plaque forming units) Zostavax will be administered subcutaneously once at the baseline visit

Outcome Measures

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Primary Outcome Measures :

1. safety [ Time Frame: 12 weeks ]
   The primary outcome of the study is assessment of adverse events, including injection site reactions and development of zoster-like lesions, following vaccination in subjects with RA compared to healthy subjects

Secondary Outcome Measures :

1. Immunogenicity [ Time Frame: 6 weeks ]
   The secondary objective of the study is immunogenicity. Specifically, the change from baseline in varicella-zoster virus-specific cell mediated immunity (assessed by IFN-g ELISpot) between subjects with RA and healthy subjects will be compared.

Eligibility Criteria

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Ages Eligible for Study:	50 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Age ≥ 50 years
• Willing and able to provide written informed consent
• History of primary varicella vaccination or positive VZV IgG antibodies
• Diagnosis of RA according to ACR criteria for > 1 year, or healthy control subject
• Stable, mild disease activity as defined by a DAS28 score of 4.0
• Current medical treatment for RA has been stable for 4 weeks prior to screening
• Acceptable immunosuppressive medications are limited to Prednisone ≤ 10 mg daily Methotrexate ≤ 20 mg weekly Hydroxychloroquine ≤ 6.5 mg/kg daily Any TNF inhibitor
• Female subjects of childbearing potential and non-sterile males must agree to use acceptable form of contraception for the duration of the study

Exclusion Criteria:

• History of receiving any VZV-containing vaccine
• History of herpes zoster reactivation (shingles) within 5 years of enrollment
• Received any vaccine within 6 weeks
• Known Hepatitis B, C or HIV virus infection
• History of drug or alcohol abuse within 1 year
• Rituximab therapy within 2 years of screening
• Cyclophosphamide within 6 months of screening
• Biologic therapy: TNF inhibitors with longer half-lives (infliximab, golimumab, etc), or other non-TNF biologic therapies (IL-1 or IL-6 inhibition, or CTLA-4Ig)
• Use of mycophenolate mofetil within 3 months of screening
• History of receiving immunoglobulin or other blood product within 3 months of screening
• Allergic reaction, intolerance or other contraindication to use of famciclovir.
• Has received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 3 months of screening; or expects to receive another experimental/investigational agent within 6 months post immunization.
• Pregnant or lactating women
• Unwilling to use acceptable method of contraception for the duration of the study
• WBC <3.0; ANC <1500; CD4+ <200
• Proteinuria >1.5 mg/day
• Impaired renal function defined by serum Cr >1.5
• Transaminases > 2x upper limit of normal
• DAS28 > 4
• Anticipation of need to increase level of immunosuppression or add biologic therapy for 6 months following dosing.
• History of neoplastic disease within 5 years of screening, except for completely excised non-melanoma cancer of the skin or in-situ carcinoma of the uterine cervix.
• History of any hematological malignancy, current bleeding disorder or taking anticoagulant medication (heparin or warfarin).
• Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104

Sponsors and Collaborators

Oklahoma Medical Research Foundation

Investigators

Principal Investigator:	Eliza Chakravarty, MD	Oklahoma Medical Research Foundation

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier:	NCT01506661 History of Changes
Other Study ID Numbers:	OMRF11-53
First Posted:	January 10, 2012
Last Update Posted:	September 18, 2017
Last Verified:	September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Oklahoma Medical Research Foundation:

Rheumatoid arthritis; vaccination; immune response; varicella zoster

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Herpes Zoster; Chickenpox; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases	Autoimmune Diseases; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs