A Phase 2 Study For Patients With A Physician's Diagnosis Of Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00550446
• Recruitment Status: Completed
• First Posted: October 29, 2007
• Results First Posted: January 3, 2013
• Last Update Posted: January 3, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 25, 2007
• First Posted Date: October 29, 2007
• Results First Submitted Date: November 29, 2012
• Results First Posted Date: January 3, 2013
• Last Update Posted Date: January 3, 2013
• Study Start Date: September 2007
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2012)

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Week 12 ]

ACR20 response: greater than or equal to (>=) 20 % improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); 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).

• Original Primary Outcome Measures (submitted: October 25, 2007): American College of Rheumatology 20 (ACR 20) responder rate at the Week 12 visit.

Current Secondary Outcome Measures (submitted: November 29, 2012)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 2, 4, 6, 8, 10, 16, 20 and 24/Early Termination (ET) ]
  ACR20 response: 20% improvement in TJC; >=20% improvement in SJC; 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 HAQ); and CRP.
• Percentage of Participants Achieving American College of Rheumatology 50%(ACR50) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  ACR50 response: >= 50% improvement in TJC or SJC and 50% 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 HAQ); and CRP.
• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  ACR70 response: >= 70% improvement in TJC or SJC and 70% 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 HAQ); and CRP.
• Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  ACR90 response: >= 90% improvement in TJC or SJC and 90% 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 HAQ); and CRP.
• Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve [ Time Frame: Baseline up to Week 2, 4, 6, 8, 10, 12 ]
  ACR-n = calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. Area under the curve (AUC) for ACR-n is the measure of the area under the curve of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC.
• Tender Joint Count (TJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.
• Change From Baseline in Tender Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 or ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from baseline indicated an improvement.
• Swollen Joint Counts (SJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.
• Change From Baseline in Swollen Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling = 1. A negative value in change from baseline indicated an improvement.
• Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.
• Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
  Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.
• Patient Global Assessment (PtGA) of Arthritis Pain [ Time Frame: Baseline, 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
• Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.
• Physician Global Assessment (PGA) of Arthritis [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
• Change From Baseline in Physician's Global Assessment (PGA) of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
• C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 milligram per liter (mg/L) to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
• Change From Baseline in C-reactive Protein (CRP) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 mg/L to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
• Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
• Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
  DAS28-3 (CRP) was calculated from the SJC and TJC 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 less than (<) 2.6 = remission.
• Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
  DAS28-3 (CRP) was calculated from the SJC and TJC 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) <= 3.2 implied low disease activity and > 3.2 to 5.1 implied moderate to high disease activity, and < 2.6 = remission.
• Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
  DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission.
• Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR [mm/hour] and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission.
• Percentage of Participants With Disease Improvement Based on DAS28-4 (ESR) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
  Disease improvement was classified as good, moderate, and none based on improvement in DAS28-4 (ESR) from baseline and present DAS28-4 (ESR) score. Good: an improvement from baseline of >1.2 and a present score of <=3.2; none: an improvement of <=0.6 or >0.6 to <=1.2 with a present score of >5.1; remaining participants were classified as having moderate (Mod) improvement. Scores of good and moderate were considered to have therapeutic response.
• Percentage of Participants With Disease Remission Based on Normal C-reactive Protein (CRP) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
  CRP value less than or equal to upper limit of normal (ULN) implied disease remission (ULN=4.9 mg/L).
• Percentage of Participants With Disease Remission Based on DAS28-3 (CRP) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
  DAS28-3 (CRP) defined remission was classified as a score of <2.6.
• 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Baseline, Week 12, 24/ ET ]
  SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
• Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ ET ]
  SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). 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 5 Dimension (EQ-5D)-Health State Profile Utility Score [ Time Frame: Baseline, Week 12, 24/ ET ]
  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 (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
• Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D)- Health State Profile Utility Score at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ ET ]
  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 ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

Original Secondary Outcome Measures (submitted: October 25, 2007)

• The ACR 20 Responder rate will be analyzed at all other time points ACR 50 Responder rate
• ACR 70 Responder rate
• ACR 90 Responder rate
• Area under the ACR n curve
• Actual and change from baseline of the 7 individual components of the ACR 20, 50, 70, and 90 response criteria
• Actual and change from baseline in disease activity, assessed as the "Disease Activity Score (DAS) using C Reactive Protein" (DAS28 3(crp)) and the categorization of Disease Activity and rates of remission based on the changes in DAS
• Actual and change from baseline in the Health Assessment Questionnaire (HAQ DI)
• Actual and change from baseline in the SF 36 Health Questionnaire
• Actual and change from baseline in the EuroQol EQ 5D
• Actual and change from baseline in the Medical Outcomes Study (MOS) Sleep Scale
• Actual and change from baseline in the FACIT Fatigue Scale
• Safety Endpoints:
• Incidence and severity of adverse events
• Incidence and severity of clinical laboratory abnormalities
• Mean change from baseline in vital signs (blood pressure, heart rate, and oral or tympanic temperature) measurements
• Categorical summary of absolute vital signs and vital signs changes compared to baseline by subject
• Incidence and severity of adverse events after switch from adalimumab to CP 650,550 compared to CP 650,550 alone
• Exploratory Endpoints:
• Actual and change from baseline in serum IgG, IgM and IgA levels
• Actual and change from baseline in FACS lymphocyte biomarkers.

Current Other Pre-specified Outcome Measures (submitted: November 29, 2012)

• Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels [ Time Frame: Baseline, Week 24/ ET ]
  Blood samples for immunoglobulin assessments were obtained to determine IgG, IgM, and IgA levels in serum.
• Change From Baseline in Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels at Week 24 [ Time Frame: Baseline, Week 24/ ET ]
  Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgG, IgM, and IgA levels.
• Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers [ Time Frame: Baseline, Week 24/ ET ]
  The following biomarkers were assessed: Cluster of Differentiation 3 (CD3), CD4, CD8, CD19 and CD56. FACS analysis for lymphocyte subset markers were used to assess the effects of repeated doses of CP-690,550.
• Change From Baseline in Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers at Week 24 [ Time Frame: Baseline, Week 24/ ET ]
  The following biomarkers were assessed: CD3, CD4, CD8, CD19 and CD56. FACS analysis for lymphocyte subset markers were used to assess the effects of repeated doses of CP-690,550.
• Medical Outcome Study- Sleep Scale (MOS-SS) [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
  Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 sub scales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0)and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute.
• Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
  Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (A SOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range: 0-100); sleep quantity (Qua) (range: 0-24), and optimal (Opt) sleep (yes: 1, no: 0) and 9 item index measures of sleep disturbance were constructed to provide 2 composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range*100); total score range: 0 to 100; higher score = greater intensity of attribute.
• Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
  FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.
• Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
  FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Study For Patients With A Physician's Diagnosis Of Rheumatoid Arthritis
• Official Title: A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis
• Brief Summary: The purpose of this study is to determine the effectiveness and safety, over 6 months, of 5 doses of CP-690,550 for the treatment of adults with active rheumatoid arthritis. Five out of seven subjects will receive CP-690,550. One out of seven will receive adalimumab (Humira®) and one out of seven will only receive inactive substances (placebo.)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid

Intervention

• Drug: Adalimumab
  40mg subcutaneous injections every other week for 6 injections during week 0-10 with oral placebo BID. Subjects switched to CP-690,550 at week 12.
• Drug: CP-690-550
  15 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)
• Drug: CP-690-550
  10 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)
• Drug: CP-690-550
  5 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)
• Drug: CP-690,550
  3 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)
• Drug: CP-690,550
  1 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)
• Drug: Placebo
  Placebo by mouth plus 6 placebo subcutaneous injections (week 0-10)

Study Arms

• Active Comparator: 1
  Intervention: Drug: Adalimumab
• Experimental: 2
  Intervention: Drug: CP-690-550
• Experimental: 3
  Intervention: Drug: CP-690-550
• Experimental: 4
  Intervention: Drug: CP-690-550
• Experimental: 5
  Intervention: Drug: CP-690,550
• Experimental: 6
  Intervention: Drug: CP-690,550
• Placebo Comparator: 7
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.
• 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. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Suzuki M, Shoji S, Miyoshi S, Krishnaswami S. Model-Based Comparison of Dose-Response Profiles of Tofacitinib in Japanese Versus Western Rheumatoid Arthritis Patients. J Clin Pharmacol. 2020 Feb;60(2):198-208. doi: 10.1002/jcph.1514. Epub 2019 Sep 12.
• Mariette X, Chen C, Biswas P, Kwok K, Boy MG. Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program. Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421. Epub 2018 Apr 2.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Wallenstein GV, Kanik KS, Wilkinson B, Cohen S, Cutolo M, Fleischmann RM, Genovese MC, Gomez Reino J, Gruben D, Kremer J, Krishnaswami S, Lee EB, Pascual-Ramos V, Strand V, Zwillich SH. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016 May-Jun;34(3):430-42. Epub 2016 Apr 28.
• Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum In: Ann Rheum Dis. 2017 Mar;76(3):611.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, Wilkinson BE, Zwillich SH. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012 Mar;64(3):617-29. doi: 10.1002/art.33383.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 29, 2012): 386
• Original Enrollment (submitted: October 25, 2007): 350
• Actual Study Completion Date: January 2009
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects must have active rheumatoid arthritis
• Subjects must have failed at least 1 disease modifying anti-rheumatic drug (DMARD)
• Subjects must not be currently taking any DMARD other than an antimalarial

Exclusion Criteria:

• Subjects who discontinued any previous TNF inhibitor therapy for either lack of benefit or safety.
• Subjects who previously received adalimumab (Humira®) therapy for any reason.
• Subjects with evidence of blood disorders, chronic infections or untreated tuberculosis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Bulgaria, Chile, Croatia, Czech Republic, Germany, Greece, Hungary, Italy, Korea, Republic of, Mexico, Romania, Slovakia, Ukraine, United States

Administrative Information

• NCT Number: NCT00550446
• Other Study ID Numbers: A3921035
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2012