A Study to Assess Immune Response Following Zoster Vaccination to Subjects With Rheumatoid Arthritis Receiving Tofacitinib or Placebo With Background Methotrexate

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study To Assess The Immune Response Following Administration Of Zoster Vaccine To Subjects With Rheumatoid Arthritis Receiving Tofacitinib (Cp-690,550) Or Placebo With Background Methotrexate Treatment

This study will evaluate immune response following administration of zoster vaccine in subjects with rheumatoid arthritis who are receiving background methotrexate and initiate 5 mg twice daily of tofacitinib or placebo for tofacitinib 2 to 3 weeks following vaccination.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tofacitinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • California
    • Los Angeles, California, United States, 90095
      • UCLA David Geffen School of Medicine
    • Los Angeles, California, United States, 90095
      • Drug Shipping Address (IRB# 14-000826) Ronald Regan
    • Santa Maria, California, United States, 93454
      • Pacific Arthritis Center Medical Group
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33173
      • Center for Arthritis and Rheumatic Diseases
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Pinellas Park, Florida, United States, 33782
      • DMI Research, Inc.
    • Port Richey, Florida, United States, 34668
      • Gulf Coast Medical Center
    • Port Richey, Florida, United States, 34668
      • Florida Arthritis and Osteoporosis Center
    • Saint Petersburg, Florida, United States, 33705
      • Suncoast Medical Clinic
    • Saint Petersburg, Florida, United States, 33710
      • Sun Coast Medical Clinic
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
    • Tampa, Florida, United States, 33614
      • Health Point Medical Group, Inc.
  • Illinois
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Diagnostic Rheumatology And Research, PC
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis Treatment Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12206
      • The Center For Rheumatology, Llp
    • Orchard Park, New York, United States, 14127
      • Buffalo Rheumatology and Medicine, PLLC
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory, LLC
    • Hickory, North Carolina, United States, 28602
      • Piedmont Rheumatology, P.A
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury, LLC
    • Salisbury, North Carolina, United States, 28147
      • Novant Health Imaging Julian Road
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, Pc
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading LLP
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Palmetto Clinical Trial Services, LLC
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Arthritis Clinic
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
    • Knoxville, Tennessee, United States, 37909-1907
      • Rheumatology Consultants, PLLC
  • Texas
    • Allen, Texas, United States, 75013
      • Office of John P. Lavery, MD, PA
    • Dallas, Texas, United States, 75231
      • Baylor Research Institute Arthritis Care and Research Center
  • Washington
    • Vancouver, Washington, United States, 98664
      • The Vancouver Clinic (Drug Shipment Only)
    • Vancouver, Washington, United States, 98664
      • The Vancouver Clinic, Inc, PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have moderate to severe rheumatoid arthritis inadequately controlled by methotrexate as defined by the American College of Rheumatology (ACR) classification criteria for Rheumatoid arthritis, painful and swollen joint counts and C-reactive protein (CRP).
• Screening CRP >3 mg/L or CDAI score > 10 at screening or at baseline before vaccination.
• Subjects must have active disease at screening and baseline.
• Must be at least 50 years of age or older.

Exclusion Criteria:

• History of receiving any varicella-zoster virus vaccine
• Receipt of any vaccines within 6 weeks of first dose of study treatment.
• Subjects with current infections or history of infections.
• History of recurrent (more than one episode) of herpes zoster or disseminated (a single episode) of herpes zoster or disseminated (a single episode) of herpes simplex.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib 5 mg BID (oral) (70 subjects); Zoster vaccine will be administered to subjects on background methotrexate; treatment with 5 mg tofacitinib twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks.	Drug: Tofacitinib; 5 mg twice daily of tofacitinib with background methotrexate for 12 weeks
Placebo Comparator: Placebo tofacitinib BID (oral) (70 subjects); Zoster vaccine will be administered to subjects on background methotrexate; treatment with placebo twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks.	Drug: Placebo; Placebo tablets twice daily with background methotrexate for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Immunoglobulin G (IgG) Levels at Week 4	VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).	Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12		Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination)
Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12	The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values.	Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)
Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12	VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (>=)1.5 was defined as a responder.	Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 16 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.	Baseline up to Week 16
Number of Participants With Zoster Vaccine-Related AEs by System Organ Class	Zoster vaccine-related AEs included General Disorders and Administration Site Conditions (injection site erythema, pain, pruritis, rash, swelling; vaccination site erythema, pruritus, rash), Infections and Infestations (disseminated herpes zoster), and Musculoskeletal and Connective Tissue Disorders (myalgia). All zoster vaccine-related AEs were mild, except for the herpes zoster AE classified under Infections and Infestations, which was moderate in severity.	Baseline up to Week 16
Number of Participants With Clinical Herpes Zoster Events by Severity	Clinical herpes is manifested as mild, moderate, or severe disseminated herpes zoster.	Baseline up to Week 16
Number of Participants With Clinically Significant Abnormal Laboratory Parameters	Participants with the following abnormalities were discontinued from the study: 2 sequential absolute neutrophil counts (ANC) <1000/mm^3; 2 sequential hemoglobin values <8.0 g/dL or decreases of >30% from baseline value; 2 sequential absolute lymphocyte count <500/mm^3; 2 sequential platelet counts <75,000/mm^3; 2 sequential alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >=3 times the upper limit of normal (X ULN) with a total bilirubin value >=2X ULN, elevated international normalized ratio (INR), or accompanied by signs/symptoms consistent with hepatic injury; 2 sequential ALT or AST elevations >=5X ULN regardless of total bilirubin or accompanying symptoms; confirmed increases in serum creatinine (SCr) >50% over the average of screening and baseline values; a confirmed positive urine pregnancy test or refusal to use appropriate contraception in a woman of childbearing potential.	Baseline up to Week 16

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
• Winthrop KL, Wouters AG, Choy EH, Soma K, Hodge JA, Nduaka CI, Biswas P, Needle E, Passador S, Mojcik CF, Rigby WF. The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial. Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187. Epub 2017 Sep 6.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: May 22, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921237; 2014-000706-34 (EudraCT Number)