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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01164579
First received: July 15, 2010
Last updated: April 21, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Tasocitinib plus Methotrexate
Drug: Tofacitinib plus placebo methotrexate
Drug: Placebo tofacitinib plus Methotrexate
Phase 2

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: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis [ Time Frame: Months 1, 6, and 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 109
Study Start Date: October 2010
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tofacitinib (CP 690,550) 10 mg BID plus MTX 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
Experimental: Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX 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.
Active Comparator: Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk 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

  Eligibility

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

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.
  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: NCT01164579

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

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01164579     History of Changes
Other Study ID Numbers: A3921068, 2010-020890-18
Study First Received: July 15, 2010
Results First Received: November 5, 2014
Last Updated: April 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Early Rheumatoid Arthritis
Joint Structure
Magnetic Resonance Imaging
Janus Kinase (JAK) Inhibitor
Tasocitinib
Tofacitinib

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

ClinicalTrials.gov processed this record on July 05, 2015