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Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)

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ClinicalTrials.gov Identifier: NCT01164579
Recruitment Status : Completed
First Posted : July 16, 2010
Results First Posted : April 22, 2015
Last Update Posted : April 22, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 15, 2010
First Posted Date  ICMJE July 16, 2010
Results First Submitted Date  ICMJE November 5, 2014
Results First Posted Date  ICMJE April 22, 2015
Last Update Posted Date April 22, 2015
Study Start Date  ICMJE October 2010
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
  • Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis [ Time Frame: Month 3 ]
    Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.
  • Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema [ Time Frame: Month 6 ]
    Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2010)
Change from baseline in OMERACT RAMRIS wrist synovitis. [ Time Frame: 3 months ]
Change History Complete list of historical versions of study NCT01164579 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
  • Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis [ Time Frame: Months 1, 6, and 12 ]
    Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement.
  • Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP [ Time Frame: Months 1, 3, and 12 ]
    Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€"3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€"33% of bone edematous; 2: 34â€"66% of bone edematous; 3: 67â€"100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity.
  • Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions [ Time Frame: Months 1, 3, 6, and 12 ]
    Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity.
  • Modified Total Sharp Score (mTSS) at Months 6 and 12 [ Time Frame: Months 6 and 12 ]
    Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Change From Baseline to Months 6 and 12 in mTSS [ Time Frame: Months 6 and 12 ]
    Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) + erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Joint Space Narrowing (JSN) Scores at Months 6 and 12 [ Time Frame: Months 6 and 12 ]
    JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Change From Baseline to Months 6 and 12 in JSN Scores [ Time Frame: Months 6 and 12 ]
    JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Erosion Scores at Months 6 and 12 [ Time Frame: Months 6 and 12 ]
    Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Change From Baseline to Months 6 and 12 in Erosion Score [ Time Frame: Months 6 and 12 ]
    Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
  • Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    ACR20 response: greater than or equal to (≥)20% 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's Assessment of Pain; Participant's 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).
  • Percentage of Participants With an ACR 50% Improvement (ACR50) Response [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    ACR50 response: ≥ 50% 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) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit.
  • Percentage of Participants With an ACR 70% Improvement (ACR70) Response [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    ACR70 response: ≥70% 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) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit.
  • Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) [ Time Frame: Baseline and Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<)2.6 = remission.
  • Change From Baseline in DAS28-3 (CRP) [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity.
  • Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) [ Time Frame: Baseline and Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) <2.6 = remission.
  • Change From Baseline in DAS28-4 (ESR) [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour [mm/hour]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity.
  • Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).
  • Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity.
  • Percentage of Participants With DAS28-3 (CRP) Score <2.6 [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) <2.6 implied remission.
  • Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL).
  • Percentage of Participants With DAS28-4 (ESR) ≤3.2 [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity.
  • Percentage of Participants With DAS28-4 (ESR) <2.6 [ Time Frame: Months 1, 2, 3, 6, 9, and 12 ]
    DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) <2.6 implied remission.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2010)
  • Change from baseline in OMERACT RAMRIS wrist synovitis (range 0 9) at all assessed time points. [ Time Frame: 12 months ]
  • Change from baseline in OMERACT RAMRIS bone marrow edema (range 0 - 69) and erosions (MCPs 2 5 and wrist joints, range 0 230) at all assessed time points. [ Time Frame: 12 months ]
  • Modified total Sharp scores, joint space narrowing and erosion scores as ascertained from PA hand and anteroposterior AP foot radiographs obtained at baseline, 6 and 12 months, scored by a central facility. [ Time Frame: 12 months ]
  • Proportion of subjects achieving ACR 20, ACR 50 and ACR 70 at all time points. [ Time Frame: 12 months ]
  • Actual and change from baseline in disease activity, assessed as DAS28 3 CRP and DAS28 4 ESR and the categorization of disease activity based on DAS at all time points. [ Time Frame: 12 months ]
  • Incidence and severity of AEs. [ Time Frame: 12 months ]
  • Incidence and severity of clinical laboratory abnormalities. [ Time Frame: 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA)
Official Title  ICMJE An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis
Brief Summary Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Tasocitinib plus Methotrexate
    Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months
  • Drug: Tofacitinib plus placebo methotrexate
    Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1.
  • Drug: Placebo tofacitinib plus Methotrexate
    Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib
Study Arms  ICMJE
  • Experimental: Tofacitinib (CP 690,550) 10 mg BID plus MTX
    Intervention: Drug: Tasocitinib plus Methotrexate
  • Experimental: Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX
    Intervention: Drug: Tofacitinib plus placebo methotrexate
  • Active Comparator: Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk
    Intervention: Drug: Placebo tofacitinib plus Methotrexate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 21, 2015)
109
Original Estimated Enrollment  ICMJE
 (submitted: July 15, 2010)
100
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients with moderate to severe early rheumatoid arthritis (< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive.

Exclusion Criteria:

  • Pregnant or lactating patients;
  • Patients with renal or hepatic impairment or other severe or progressing disease;
  • Patients with contraindication to magnetic resonance imaging with gadolinium contrast.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Chile,   Croatia,   Czech Republic,   Hungary,   Mexico,   Poland,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01164579
Other Study ID Numbers  ICMJE A3921068
2010-020890-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP