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

NCT02147587 | Completed Phase 2 Results DMC

• 2 other identifiers: A39212372014-000706-34
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 36

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

  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

  Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)

Other Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Baseline up to Week 16

• Number of Participants With Zoster Vaccine-Related AEs by System Organ Class

  Baseline up to Week 16

• Number of Participants With Clinical Herpes Zoster Events by Severity

  Baseline up to Week 16

Study Arms (2)

Tofacitinib 5 mg BID (oral) (70 subjects)

EXPERIMENTAL

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

Placebo tofacitinib BID (oral) (70 subjects)

PLACEBO COMPARATOR

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

Interventions

Tofacitinib DRUG

5 mg twice daily of tofacitinib with background methotrexate for 12 weeks

Tofacitinib 5 mg BID (oral) (70 subjects)

Placebo DRUG

Placebo tablets twice daily with background methotrexate for 12 weeks

Placebo tofacitinib BID (oral) (70 subjects)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (36)

NEA Baptist Clinic

Jonesboro, Arkansas, 72401, United States

Location

Drug Shipping Address (IRB# 14-000826) Ronald Regan

Los Angeles, California, 90095, United States

Location

UCLA David Geffen School of Medicine

Los Angeles, California, 90095, United States

Location

Pacific Arthritis Center Medical Group

Santa Maria, California, 93454, United States

Location

Inland Rheumatology Clinical Trials, Inc.

Upland, California, 91786, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Center for Arthritis and Rheumatic Diseases

Miami, Florida, 33173, United States

Location

Suncoast Clinical Research, Inc.

New Port Richey, Florida, 34652, United States

Location

DMI Research, Inc.

Pinellas Park, Florida, 33782, United States

Location

Florida Arthritis and Osteoporosis Center

Port Richey, Florida, 34668, United States

Location

Gulf Coast Medical Center

Port Richey, Florida, 34668, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

Suncoast Medical Clinic

St. Petersburg, Florida, 33705, United States

Location

Sun Coast Medical Clinic

St. Petersburg, Florida, 33710, United States

Location

Health Point Medical Group, Inc.

Tampa, Florida, 33614, United States

Location

Deerbrook Medical Associates

Vernon Hills, Illinois, 60061, United States

Location

Diagnostic Rheumatology And Research, PC

Indianapolis, Indiana, 46227, United States

Location

Arthritis Treatment Center

Frederick, Maryland, 21702, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

The Center for Rheumatology, LLP

Albany, New York, 12206, United States

Location

Buffalo Rheumatology and Medicine, PLLC

Orchard Park, New York, 14127, United States

Location

Piedmont Rheumatology, P.A

Hickory, North Carolina, 28602, United States

Location

PMG Research of Hickory, LLC

Hickory, North Carolina, 28602, United States

Location

PMG Research of Salisbury, LLC

Salisbury, North Carolina, 28144, United States

Location

Novant Health Imaging Julian Road

Salisbury, North Carolina, 28147, United States

Location

East Penn Rheumatology Associates, PC

Bethlehem, Pennsylvania, 18015, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Clinical Research Center of Reading LLP

Wyomissing, Pennsylvania, 19610, United States

Location

Palmetto Clinical Trial Services, LLC

Greenville, South Carolina, 29601, United States

Location

Arthritis Clinic

Jackson, Tennessee, 38305, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Rheumatology Consultants, PLLC

Knoxville, Tennessee, 37909-1907, United States

Location

Office of John P. Lavery, MD, PA

Allen, Texas, 75013, United States

Location

Baylor Research Institute Arthritis Care and Research Center

Dallas, Texas, 75231, United States

Location

The Vancouver Clinic (Drug Shipment Only)

Vancouver, Washington, 98664, United States

Location

The Vancouver Clinic, Inc, PS

Vancouver, Washington, 98664, United States

Location

Related Publications (9)

• Hetland ML, Strangfeld A, Bonfanti G, Soudis D, Deuring JJ, Edwards RA. Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib. Arthritis Res Ther. 2024 Aug 27;26(1):153. doi: 10.1186/s13075-024-03376-9.

  PMID: 39192350 DERIVED

• Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.

  PMID: 36931693 DERIVED

• Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.

  PMID: 36601090 DERIVED

• Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.

  PMID: 36600185 DERIVED

• Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.

  PMID: 36526796 DERIVED

• 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.

  PMID: 34870800 DERIVED

• 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.

  PMID: 33127856 DERIVED

• 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.

  PMID: 32816215 DERIVED

• 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.

  PMID: 28845577 DERIVED

Related Links

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

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2014
• First Posted: May 28, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: April 11, 2018
• Results First Posted: April 11, 2018

Record last verified: 2018-03

Locations

US (36)