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Safety and Tolerability of Herpes Zoster Vaccine Rheumatologic Patients

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ClinicalTrials.gov Identifier: NCT03016884
Recruitment Status : Recruiting
First Posted : January 11, 2017
Last Update Posted : January 30, 2018
Sponsor:
Information provided by (Responsible Party):
HaEmek Medical Center, Israel

Brief Summary:

The reactivation of varicella zoster virus (VZV) (herpes zoster (HZ)) is of substantial public health concern. Updated ACR recommendations for RA treatment suggest that RA patients aged ≥ 50 years should be vaccinated before receiving biologic or tofacitinib therapy. The Investigators therefore propose a prospective study to evaluate the safety, tolerability, and immunogenicity of a zoster vaccine (Zostavax) in patients with RA, administered at least 2 weeks prior to initiation of anti-TNF biologic and tofacitinib therapy for RA.

This is a 6-week open-label prospective multi-center study evaluating the safety, tolerability, and immunogenicity of Zostavax vaccine in the RA population prior to initiation of biologic/tofacitinib therapy for RA. VZV-specific immune response to vaccine in RA patients will be compared to healthy control subjects ≥ 50 years immunized with Zostavax.


Condition or disease Intervention/treatment Phase
Herpes Zoster Biological: Zostavax vaccine Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Safety and Tolerability of Herpes Zoster Vaccine in Patients With Rheumatoid Arthritis Immunized Prior to Biologics and Tofacitinib Therapy Initiation
Actual Study Start Date : January 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shingles

Arm Intervention/treatment
Experimental: RA patients
RA patients will be administered Zostavax vaccine once 2 weeks before initiation of bDMARD, and be monitored accordingly
Biological: Zostavax vaccine
After the screening, the eligible patients who provided the informed consent, will be administered the zoster vaccine.
Other Name: ZOSTAVAX® (Zoster Vaccine Live)

Experimental: Healthy Controls
healthy control patients will be administered Zostavax vaccine and be monitored accordingly
Biological: Zostavax vaccine
After the screening, the eligible patients who provided the informed consent, will be administered the zoster vaccine.
Other Name: ZOSTAVAX® (Zoster Vaccine Live)




Primary Outcome Measures :
  1. Number of patients with Injection site adverse reactions [ Time Frame: 6 weeks ]
    collecting number of patients with injection site adverse reactions defined as: Local pain/erythema/swelling/pruritus/warmth/hematoma/induration will be assessed by the investigators at follow up visit, and will be asked by phone call.

  2. Number of patients with Hypersensitivity [ Time Frame: 6 weeks ]
    collecting number of patients with hypersensitivity adverse reactions defined as: Any immediate systemic reactions such as anaphylactic reaction, fever, low blood pressure, drug induced rash or urticaria, nausea and vomiting, diarrhea data will be collected at the visit of injection administration, and by phone call 2 weeks past the vaccination

  3. number of patients with Post vaccination non-injection-site zoster-like and varicella-like rashes [ Time Frame: 6 weeks ]
    collecting number of patients with non-injection-site zoster-like and varicella-like rash will be defined as adverse reaction. will be assessed by investigator by phone follow up and at 6 weeks follow up meeting.

  4. Number of patients with Post vaccination herpes zoster occurrence [ Time Frame: 6 weeks ]
    collecting number of patients with Post vaccination herpes zoster occurrence will be defined as adverse reaction. will be assessed by investigator by phone follow up and at 6 weeks follow up meeting.


Secondary Outcome Measures :
  1. Immunogenicity measured by varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) [ Time Frame: 6 weeks ]
    of 15 cc blood only will be taken at two visits: pre-vaccination and post-vaccination (6 weeks). Serum will be separated, aliquoted and stored frozen at -20°C until analysis. The serum samples will be stored and tested in the TASMC Laboratory for Arthritis Research. VZV antibody titers will be measured by commercially available ELISA kits. Any other analyses of the serum samples in the future will only be performed after obtaining permission from the institutional ethics committee, as required by law. No genetic test will be performed. The serum samples will not be taken outside of the Tel Aviv Medical Center, unless specific permission is obtained from the institutional ethics committee in the future. Samples of 15 cc blood only will be taken at two visits: pre-vaccination and post-vaccination (6 weeks). Serum will be separated, aliquoted and stored frozen at -20°C until analysis. The serum samples will be stored and tested in the TASMC Laboratory for Arthritis Research. VZV antibody

  2. Tender and Swollen Joint Count (28 joint count) [ Time Frame: 6 weeks ]

    Twenty-eight (28) joints will be assessed by a physician to determine the number of joints that are considered tender/painful. The response to pressure/motion on each joint will be assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial joints). These joints will be further assessed for swelling using the same scale.

    The 28 joints to be assessed are the shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees. Artificial joints will not be assessed.


  3. Patient Assessment of Arthritis Pain [ Time Frame: 6 weeks ]
    Participants will assess the severity of their arthritis pain using a 100 mm visual analog scale (VAS) placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain.

  4. Patient Global Assessment of Arthritis [ Time Frame: 6 weeks ]
    Participants will answer the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The subject's response will be recorded using a 100 mm VAS

  5. Physician Global Assessment of Arthritis [ Time Frame: 6 weeks ]
    The physician will assess how the subject's overall arthritis appears at the time of the visit. This is an evaluation based on the subject's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The Investigator's response will be recorded using a 100 mm VAS.

  6. Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: 6 weeks ]
    The HAQ-DI assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities.13 Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. The form should then be checked by the site staff for completeness.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

For RA arm:

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
  2. Patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA scheduled for a biologic or small molecule therapy (80% candidates for etanercept or tofacitinib therapies.)
  3. Only subjects who are ≥ 50 years old will be administered the zoster vaccine.
  4. Subjects who are willing and able to comply with scheduled visits and other study procedures
  5. Patients on biologics may participate after a washout period as indicated below :

    1. Etanercept : 2 weeks
    2. Infliximab, Golimumab, Adalimumab : 35 days
    3. Tocilizumab and Abatacept SC : 2 weeks
    4. Tocilizumab and Abatacept IV : 35 days

Exclusion Criteria:

  1. History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.
  2. Previous vaccination with any VZV-containing vaccine.
  3. Any type of malignancy, ongoing chemotherapy or radiation therapy.
  4. Patients who underwent solid organ transplantation.
  5. Patients with AIDS or clinical manifestations of HIV
  6. Patients treated with a TNFa inhibitor at the time of recruitment or patients within a year of rituximab administration.
  7. Patients receiving daily corticosteroid therapy with a dose ≥10 mg/day of prednisone (or equivalent) for ≥ 14 days and/or methotrexate at the dose above 0.4 mg per kg per week.
  8. Patients with an active herpes zoster infection or previous herpes zoster less than 6 months before recruitment.
  9. Vaccination with any live vaccine within 4 weeks prevaccination, any inactivated vaccine within 7 days prevaccination, or either during the study period.
  10. Blood products transfusion within 5 months prior to vaccination through the study period.
  11. Patients with active tuberculosis.
  12. History of Guillain-Barre Syndrome

for healthy arm: Inclusion subjects who are ≥ 50 years old will be administered the zoster vaccine.

Exclusion

  1. History of past or present autoimmune diseases
  2. History or current use of immunosuppressive drugs
  3. History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.
  4. .Previous vaccination with any VZV-containing vaccine.
  5. Any type of malignancy, ongoing chemotherapy or radiation therapy.
  6. History of underwent solid organ transplantation.
  7. Active herpes zoster infection or previous herpes zoster less than 6 months before recruitment.
  8. Vaccination with any live vaccine within 4 weeks prevaccination, any inactivated vaccine within 7 days prevaccination, or either during the study period.
  9. Blood products transfusion within 5 months prior to vaccination through the study period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03016884


Contacts
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Contact: Ori Elkayam, MD +972-3-6973243 orie@tlvmc.gov.il
Contact: Amir Bieber, MD +972-4-6494354 amir.bieber@gmail.com

Locations
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Israel
Ha'Emek Medical center, Unit of Rheumatology Recruiting
Afula, Israel
Contact: Amir Bieber, MD    972-52-6054854    amir.bieber@gmail.com   
Carmel Medical Center Recruiting
Haifa, Israel
Contact: Devi Zissman, MD    972-4-8250486      
Tel Aviv Medical Center, Unit pf Rheumatology Recruiting
Tel Aviv, Israel
Contact: Ori Elkayam, MD    972-3-6973248    rheumatology@tlvmc.gov.il   
Sponsors and Collaborators
HaEmek Medical Center, Israel

Publications:

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Responsible Party: HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT03016884     History of Changes
Other Study ID Numbers: 142-016-EMC
First Posted: January 11, 2017    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by HaEmek Medical Center, Israel:
Herpes Zoster
anti TNF alpha
tofacitinib
Rheumatoid Arthritis

Additional relevant MeSH terms:
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Herpes Zoster
Varicella Zoster Virus Infection
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Vaccines
Tofacitinib
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action