Efficacy And Safety Of Tofacitinib In Psoriatic Arthritis: Comparator Study (OPAL BROADEN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01877668
First received: June 12, 2013
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

This is a 12 month study investigating the effectiveness and safety of tofactinib in treating the signs and symptoms, improving physical function and preserving bone structure in patients with active psoriatic arthritis and had inadequate response to a traditional, non-biologic disease modifying anti-rheumatic drug. Adalimumab is use as a comparator.


Condition Intervention Phase
Psoriatic Arthritis
Drug: Tofacitinib 5 mg BID
Drug: Tofacitinib 10 mg BID
Drug: Adalimumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of Tofacitinib (CP-690,550) Or Adalimumab In Subjects With Active Psoriatic Arthritis

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

  • Score on Health Assessment Questionaire-Disability Index [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    Score on Health Assessment Questionaire-Disability Index patient reported outcome


Secondary Outcome Measures:
  • Change from baseline Modified Total Sharp Score (mTSS) at Month 12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation minus score at Baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 2, Month 1, Month 2, Month 4, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).

  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week2, Month 1, Month 2, Month 4, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.

  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 2. Month 1, Month 2, Month 4, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.

  • ACR response criteria components [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    HAQ-DI, CRP, Patient's Assessment of Arthritis Pain,

  • Number of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    PsARC is comprised of 4 clinical improvement criteria: 1 unit (0-5 Likert scale) improvement on the Physician Global Assessment (PGA); 20% (0-100 scale) improvement on the participant assessments; and 30% reduction in the number of tender joints; and 30% reduction in the number of swollen joints. To achieve a clinical response, the participant must improve in 2 of the 4 PsARC criteria, 1 of which has to be the number of tender or swollen joints and none of the 4 scores could worsen.

  • Physician Global Assessment (PGA) of Psoriasis Score [ Time Frame: Month 1, Month 3, Month 6, MOnth 9, Month 12 ] [ Designated as safety issue: No ]
    PGA of Psoriasis scale ranges from 0 (no psoriasis) to 5 (severe disease). 'Clear' and "Almost clear' includes all participants who were scored as a 0 or 1.

  • Psoriasis Area and Severity Index (PASI) [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    PASI score ranges from 0 to 72, with higher scores representing greater severity of psoriasis

  • Dactylitis Severity Score [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    Dactylitis score based upon digit tenderness for each digit of hands and feet, ranges from 0-60

  • Enthesitis score based upon SPARCC (Spondyloarthritis Research Consortium) and Leeds indices [ Time Frame: Month 1, Month 3, MOnth 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    Enthesitis score based upon presence/absence of enthesitis at 16 sites (SPARCC) or 6 sites (Leeds)

  • 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Euro Quality of Life (EQ-5D)- Health State Profile Utility Score at Week X [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (

  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    FACIT: participant rated questionnaire to assess fatigue

  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Month 1, Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: No ]
    BASDAI is a validated self assessment too used to determine disease activity in participants with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale of 0-10 (0=none and 10=very severe) participants answer 6 questions measuring discomfort, pain, and fatigue. The final BASDAI score averages the individual assessments for a final score ranging 0-10.


Estimated Enrollment: 400
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tofacitinib 5 mgBID x 12 months Drug: Tofacitinib 5 mg BID
Tofacitinib orally (po) 1 tablet of 5 mg and placebo po 1 tablet BID x 12 months Placebo injections subcu every 2 weeks x 12 months
Experimental: Tofacitinib 10 mg BID x 12 months Drug: Tofacitinib 10 mg BID
Tofacitinib po 2 tablets of 5 mg BID x 12 months Placebo injections subcu every 2 weeks x 12 months
Active Comparator: Adalimumab 40 mg q2 weeks x 12 months Drug: Adalimumab
Placebo po 2 tablets BIDx 12 months Adalimumab 40 mg subcu injections every 2 weeks x 12 months
Placebo Comparator: Placebo x3 months, then tofacitinib 5 mg BIDx 9 months Drug: Placebo
Placebo po 2 tablets BIDx 3 months followed by tofacitinib po 1 tablet of 5 mg and placebo po 1 tablet BID x 9 months Placebo injections every 2 weeks x 12 months
Placebo Comparator: Placebo x 3 months, then tofacitinib 10 mg BID x 9 months Drug: Placebo
Placebo po 2 tablets BIDx 3 months followed by tofacitinib po 2 tablets (5 mg) BID x 9 months Placebo injections every 2 weeks x 12 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females, aged >= 18 years at time of consent.
  • Have a diagnosis of Psoriatic arthritis (PsA) of >= 6 months
  • Meet the Classification Criteria of PsA (CASPAR) at time of screening
  • Must not have been adequately treated with a a traditional non-biologic disease modifying anti-rheumatic drug (DMARD).
  • Concurrent treatment with methotrexate, leflunomide, or sulfasalazine allowed and required
  • Must not have taken a biologic Tumour Necrosis Factor Inhibitor
  • Must have 3 or more swollen joints AND 3 or more tender joints
  • Must have active psoriasis skin lesions

Exclusion Criteria:

  • Have non-plaque forms of psoriasis, eg erythrodermic, guttate or pustular, with the exception of nail psoriasis which is allowed
  • Pregnant or breast feeding, females of child-bearing potential not using highly effective contraception
  • New York Heart Association Class III and IV congestive heart failure
  • History of hypersensitivity or infusion reaction to biologic agents
  • Infection with HIV, hepatitis B virus, hepatitis C virus, or other chronic infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01877668

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Show 125 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01877668     History of Changes
Other Study ID Numbers: A3921091
Study First Received: June 12, 2013
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
psoriatic arthritis
radiographic changes
active comparator
tofacitinib

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Adalimumab
Tofacitinib
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014