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

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ClinicalTrials.gov Identifier: NCT02147587
Recruitment Status : Completed
First Posted : May 28, 2014
Results First Posted : April 11, 2018
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Tofacitinib Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


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




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


Secondary Outcome Measures :
  1. Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12 [ Time Frame: Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination) ]
  2. Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12 [ Time Frame: Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination) ]
    The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values.

  3. Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12 [ Time Frame: Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination) ]
    VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (>=)1.5 was defined as a responder.


Other Outcome Measures:
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 16 ]
    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.

  2. Number of Participants With Zoster Vaccine-Related AEs by System Organ Class [ Time Frame: Baseline up to Week 16 ]
    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.

  3. Number of Participants With Clinical Herpes Zoster Events by Severity [ Time Frame: Baseline up to Week 16 ]
    Clinical herpes is manifested as mild, moderate, or severe disseminated herpes zoster.

  4. Number of Participants With Clinically Significant Abnormal Laboratory Parameters [ Time Frame: Baseline up to Week 16 ]
    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.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT02147587


  Show 36 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02147587     History of Changes
Other Study ID Numbers: A3921237
2014-000706-34 ( EudraCT Number )
First Posted: May 28, 2014    Key Record Dates
Results First Posted: April 11, 2018
Last Update Posted: April 11, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Vaccines
Methotrexate
Tofacitinib
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors