Safety and Tolerability of Herpes Zoster Vaccine Rheumatologic Patients

NCT03016884 | Unknown Phase 4

• 1 other identifier: 142-016-EMC
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 3

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.

Conditions

Herpes Zoster

Keywords

Herpes Zoster; anti TNF alpha; tofacitinib; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Number of patients with Injection site adverse reactions

  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.

  6 weeks

• Number of patients with Hypersensitivity

  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

  6 weeks

• number of patients with Post vaccination non-injection-site zoster-like and varicella-like rashes

  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.

  6 weeks

• Number of patients with Post vaccination herpes zoster occurrence

  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.

  6 weeks

Secondary Outcomes (6)

• Immunogenicity measured by varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA)

  6 weeks

• Tender and Swollen Joint Count (28 joint count)

  6 weeks

• Patient Assessment of Arthritis Pain

  6 weeks

• Patient Global Assessment of Arthritis

  6 weeks

• Physician Global Assessment of Arthritis

  6 weeks

Study Arms (2)

RA patients

EXPERIMENTAL

RA patients will be administered Zostavax vaccine once 2 weeks before initiation of bDMARD, and be monitored accordingly

Biological: Zostavax vaccine

Healthy Controls

EXPERIMENTAL

healthy control patients will be administered Zostavax vaccine and be monitored accordingly

Biological: Zostavax vaccine

Interventions

Zostavax vaccine BIOLOGICAL

After the screening, the eligible patients who provided the informed consent, will be administered the zoster vaccine.

Also known as: ZOSTAVAX® (Zoster Vaccine Live)

Healthy Controls; RA patients

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.)
• Only subjects who are ≥ 50 years old will be administered the zoster vaccine.
• Subjects who are willing and able to comply with scheduled visits and other study procedures
• Patients on biologics may participate after a washout period as indicated below :
• Etanercept : 2 weeks
• Infliximab, Golimumab, Adalimumab : 35 days
• Tocilizumab and Abatacept SC : 2 weeks
• Tocilizumab and Abatacept IV : 35 days

You may not qualify if:

• History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.
• Previous vaccination with any VZV-containing vaccine.
• Any type of malignancy, ongoing chemotherapy or radiation therapy.
• Patients who underwent solid organ transplantation.
• Patients with AIDS or clinical manifestations of HIV
• Patients treated with a TNFa inhibitor at the time of recruitment or patients within a year of rituximab administration.
• 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.
• Patients with an active herpes zoster infection or previous herpes zoster less than 6 months before recruitment.
• Vaccination with any live vaccine within 4 weeks prevaccination, any inactivated vaccine within 7 days prevaccination, or either during the study period.
• Blood products transfusion within 5 months prior to vaccination through the study period.
• Patients with active tuberculosis.
• History of Guillain-Barre Syndrome
• History of past or present autoimmune diseases
• History or current use of immunosuppressive drugs
• History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (3)

Ha'Emek Medical center, Unit of Rheumatology

Afula, Israel

Location

Carmel Medical Center

Haifa, Israel

Location

Tel Aviv Medical Center, Unit pf Rheumatology

Tel Aviv, Israel

Location

Related Publications (13)

• Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA, Chan KA. The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom. Arthritis Rheum. 2007 Dec 15;57(8):1431-8. doi: 10.1002/art.23112.

  PMID: 18050184 BACKGROUND

• Schmajuk G, Trivedi AN, Solomon DH, Yelin E, Trupin L, Chakravarty EF, Yazdany J. Receipt of disease-modifying antirheumatic drugs among patients with rheumatoid arthritis in Medicare managed care plans. JAMA. 2011 Feb 2;305(5):480-6. doi: 10.1001/jama.2011.67.

  PMID: 21285425 BACKGROUND

• Widdifield J, Bernatsky S, Paterson JM, Gunraj N, Thorne JC, Pope J, Cividino A, Bombardier C. Serious infections in a population-based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013 Mar;65(3):353-61. doi: 10.1002/acr.21812.

  PMID: 22833532 BACKGROUND

• Yun H, Yang S, Chen L, Xie F, Winthrop K, Baddley JW, Saag KG, Singh J, Curtis JR. Risk of Herpes Zoster in Autoimmune and Inflammatory Diseases: Implications for Vaccination. Arthritis Rheumatol. 2016 Sep;68(9):2328-37. doi: 10.1002/art.39670.

  PMID: 26990731 BACKGROUND

• Strangfeld A, Listing J, Herzer P, Liebhaber A, Rockwitz K, Richter C, Zink A. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA. 2009 Feb 18;301(7):737-44. doi: 10.1001/jama.2009.146.

  PMID: 19224750 BACKGROUND

• Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016 Oct;75(10):1843-7. doi: 10.1136/annrheumdis-2016-209131. Epub 2016 Apr 25.

  PMID: 27113415 BACKGROUND

• Schmader KE, Levin MJ, Gnann JW Jr, McNeil SA, Vesikari T, Betts RF, Keay S, Stek JE, Bundick ND, Su SC, Zhao Y, Li X, Chan IS, Annunziato PW, Parrino J. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years. Clin Infect Dis. 2012 Apr;54(7):922-8. doi: 10.1093/cid/cir970. Epub 2012 Jan 30.

  PMID: 22291101 BACKGROUND

• Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84. doi: 10.1056/NEJMoa051016.

  PMID: 15930418 BACKGROUND

• Calabrese LH, Calabrese C, Kirchner E. The 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Should Include New Standards for Hepatitis B Screening: Comment on the Article by Singh et al. Arthritis Care Res (Hoboken). 2016 May;68(5):723-4. doi: 10.1002/acr.22865. No abstract available.

  PMID: 26866816 BACKGROUND

• Yun H, Xie F, Delzell E, Chen L, Levitan EB, Lewis JD, Saag KG, Beukelman T, Winthrop K, Baddley JW, Curtis JR. Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy. Arthritis Care Res (Hoboken). 2015 May;67(5):731-6. doi: 10.1002/acr.22470.

  PMID: 25201241 BACKGROUND

• Koshima I, Higaki H, Soeda S. Combined vascularized fibula and peroneal composite-flap transfer for severe heat-press injury of the forearm. Plast Reconstr Surg. 1991 Aug;88(2):338-41. doi: 10.1097/00006534-199108000-00030.

  PMID: 1852831 BACKGROUND

• Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O'Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39. doi: 10.1002/acr.21641. No abstract available.

  PMID: 22473917 BACKGROUND

• Russell AF, Parrino J, Fisher CL Jr, Spieler W, Stek JE, Coll KE, Su SC, Xu J, Li X, Schlienger K, Silber JL. Safety, tolerability, and immunogenicity of zoster vaccine in subjects on chronic/maintenance corticosteroids. Vaccine. 2015 Jun 17;33(27):3129-34. doi: 10.1016/j.vaccine.2015.04.090. Epub 2015 May 8.

  PMID: 25964168 BACKGROUND

MeSH Terms

Conditions

Herpes Zoster; Arthritis, Rheumatoid

Interventions

Herpes Zoster Vaccine

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chickenpox Vaccine; Herpesvirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 1, 2017
• First Posted: January 11, 2017
• Study Start: January 1, 2017
• Primary Completion: September 1, 2019
• Study Completion: July 1, 2020
• Last Updated: February 19, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3)