Comparison Of 4 CP-690,550 Doses Vs. Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis in Japan

• ClinicalTrials.gov Identifier: NCT00603512
• Recruitment Status: Completed
• First Posted: January 29, 2008
• Results First Posted: January 25, 2013
• Last Update Posted: January 25, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 17, 2008
• First Posted Date: January 29, 2008
• Results First Submitted Date: November 14, 2012
• Results First Posted Date: January 25, 2013
• Last Update Posted Date: January 25, 2013
• Study Start Date: January 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 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 percent (%) 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: January 17, 2008): American College of Rheumatology 20 (ACR20) response rates at week 12<br> [ Time Frame: at week 12 ]

Current Secondary Outcome Measures (submitted: December 16, 2012)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 1, 2, 4, 8 ]
  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 1, 2, 4, 8, 12/End of Treatment (EOT) ]
  ACR50 response: >= 50% improvement in tender or swollen joint counts 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 1, 2, 4, 8, 12/EOT ]
  ACR70 response: >= 70% improvement in tender or swollen joint counts 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 1, 2, 4, 8, 12/EOT ]
  ACR90 response: >= 90% improvement in tender or swollen joint counts 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.
• Tender Joint Count (TJC) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 (TJC) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 indicates an improvement.
• Swollen Joint Count (SJC) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 (SJC) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 indicates an improvement.
• Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 = no pain and 100 = most severe pain.
• Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 = no pain and 100 = most severe pain.
• Patient Global Assessment (PtGA) of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 = very well and 100 = very poorly.
• Change From Baseline in Patient Global Assessment of Arthritis (PtGA) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 = very well and 100 = very poorly.
• Physician Global Assessment (PGA) of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.
• Change From Baseline in Physician Global Assessment of Arthritis (PGA) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.
• Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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.
• C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  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.
• Numeric Index of American College of Rheumatology Response (ACR-n) [ Time Frame: Week 1, 2, 4, 8, 12/EOT ]
  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 Numeric Index of American College of Rheumatology Response (ACR-n) Curve [ Time Frame: Baseline up to Week 12 ]
  ACR-n = calculated for each participant by taking lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of remaining 5 components of 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. The AUC for ACR-n is measure of the area under the curve of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute AUC.
• Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint 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, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
• Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ]
  DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (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) less than or equal to (=<) 3.2 implied low disease activity, greater than (>) 3.2 to 5.1 implied moderate to high disease activity and less than (<) 2.6=remission.
• 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Baseline, Week 12/EOT ]
  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 [ Time Frame: Baseline, Week 12/EOT ]
  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, selfcare, 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.
• Medical Outcome Study- Sleep Scale (MOS-SS) [ Time Frame: Baseline, Week 2, 12/EOT ]
  Participant-rated 12 item questionnaire assess constructs of sleep over past week.7 subscales:sleep disturbance(SD),snoring(Sno),awakened short of breath(ASOB),sleep adequacy(Ade),somnolence(Som)(range:0-100);sleep quantity(Qua)(range:0-24),optimal(Opt) sleep(yes:1,no:0),9 item index measures of sleep disturbance provide composite scores:sleep problem summary(SPS),overall SP(OSP).Except Ade,Opt,Qua,higher scores=more impairment.Scores transformed(actual raw score(RS) minus lowest possible score divided by possible RS range*100);total score range:0-100;higher score=more intensity of attribute.
• Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: Baseline, Week 2, 12/EOT ]
  FACIT-F 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 Secondary Outcome Measures (submitted: January 17, 2008)

• ACR 20, 50, 70, and 90, ACR-N and area under the ACR-N cruve, Obervation values and changes from baseline of the 7 components of the ACR Core set. [ Time Frame: at multiple timepoints ]
• DAS28-3 (CRP), DAS28-4 (ESR) [ Time Frame: at multiple timepoints ]
• Quality of life assessments [ Time Frame: at week 12 ]
• Incidence and severity of AEs and lab test abnormalities, vital signs, ECG [ Time Frame: at multiple timepoints ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison Of 4 CP-690,550 Doses Vs. Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis in Japan
• Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Confirm Dose Responsiveness Following 12 Weeks of the Administration of CP-690,550 (4 Doses) or Placebo in Subjects With Active Rheumatoid Arthritis Inadequately Controlled With Methotrexate Alone
• Brief Summary: The purpose of this study is to determine the effectiveness and safety, over 3 months, of 4 dose regimens of CP-690,550, combined with methotrexate, for the treatment with active rheumatoid arthritis.
• 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: Placebo
  0 mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  10 mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  1 mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  3 mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  5 mg BID, 3 blinded tablets administered BID for 12 weeks

Study Arms

• Placebo Comparator: CP-690,550, 0mg
  Intervention: Drug: Placebo
• Experimental: CP-690,550, 10mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 1mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 3mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 5mg
  Intervention: Drug: CP-690,550

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;:
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 29, 2008): 140
• Original Estimated Enrollment (submitted: January 17, 2008): 125
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Active rheumatoid arthritis
• Inadequate response to stably dosed methotrexate

Exclusion Criteria:

• Current therapy with any DMARD or biologic other than methotrexate

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00603512
• Other Study ID Numbers: A3921039
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer
• 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: December 2012