Three Dose Levels of CP-690,550 Monotherapy Versus Placebo, Administered Orally Twice Daily (BID) for 6 Weeks

• ClinicalTrials.gov Identifier: NCT00147498
• Recruitment Status: Completed
• First Posted: September 7, 2005
• Results First Posted: January 30, 2013
• Last Update Posted: January 30, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 2, 2005
• First Posted Date: September 7, 2005
• Results First Submitted Date: November 19, 2012
• Results First Posted Date: January 30, 2013
• Last Update Posted Date: January 30, 2013
• Study Start Date: January 2005
• Actual Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2012)

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 6 [ Time Frame: Week 6 ]

ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joints count (TJC); >= 20% improvement in swollen joints 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: September 2, 2005): The American College of Rheumatology 20 (ACR 20) Responder rate at Week 6

Current Secondary Outcome Measures (submitted: December 20, 2012)

• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 1, 2, 4, and 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, 6, and 8 ]
  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 1, 2, 4, 6, and 8 ]
  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.
• Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve [ Time Frame: Baseline up to Week 6 ]
  ACR-n: calculated 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. The area under the curve (AUC) for ACR-n is the measure of the AUC of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC.
• Tender Joints Count (TJC) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 Joints Count (TJC) at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 Joints Count (SJC) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 Joints Count (SJC) at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 Global Assessment (PtGA) of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 millimeter (mm) Visual Analog Scale (VAS) where 0 mm = very well and 100 mm = very poorly.
• Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 Global Assessment of Arthritis at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.
• Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
• Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
• Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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, 6, and 8 ]
  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 100 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, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  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 100 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
• Disease Activity Score Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (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 Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 1, 2, 4, 6, and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and <2.6 = remission.
• Number of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ]
  Disease improvement was classified as good, moderate, and no change based on improvement in DAS 28-3 (CRP) from baseline and present DAS 28-3 (CRP) 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 improvement. Scores of good and moderate were considered to have therapeutic response.

• Original Secondary Outcome Measures (submitted: September 2, 2005): The American College of Rheumatology 20, 50 and 70 (ACR 20, 50 and 70) Responder rates at Weeks 1, 2, 4, 6 (except for the ACR 20) and 8
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Three Dose Levels of CP-690,550 Monotherapy Versus Placebo, Administered Orally Twice Daily (BID) for 6 Weeks
• Official Title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Compare 3 Dose Levels Of CP-690,550 Versus Placebo, Administered Orally Twice Daily (BID) For 6 Weeks, In The Treatment Of The Signs And Symptoms Of Subjects With Active Rheumatoid Arthritis
• Brief Summary: The study's objective is to compare the efficacy of 3 dose levels of oral CP-690,550 monotherapy (5 mg, 15 mg, and 30 mg twice daily [BID]) versus placebo administered over 6 weeks for the treatment of the signs and symptoms of subjects with active rheumatoid arthritis (RA).
• 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: Rheumatoid Arthritis

Intervention

• Drug: CP-690,550
  Oral tablets administered at a dose of 5 mg BID for 6 weeks
• Drug: CP-690,550
  Oral tablets administered at a dose of 15 mg BID for 6 weeks
• Drug: CP-690,550
  30 mg BID for 6 weeks
• Other: Placebo
  Placebo tablets

Study Arms

• Experimental: 5 mg BID
  CP 690,550 5 mg BID
  Intervention: Drug: CP-690,550
• Experimental: 15 mg BID
  CP 690,550 15 mg BID
  Intervention: Drug: CP-690,550
• Experimental: 30 mg BID
  Oral tablets administered at a dose of 30 mg BID for 6 weeks
  Intervention: Drug: CP-690,550
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: 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;:
• 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.
• 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.
• Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009 Jul;60(7):1895-905. doi: 10.1002/art.24567. Erratum In: Arthritis Rheum. 2012 May;64(5):1487.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 7, 2012): 264
• Original Enrollment (submitted: September 2, 2005): 312
• Actual Study Completion Date: June 2006
• Actual Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• The subject has a history of inadequate response to at least 1, but no more than 4, of the following DMARDs: sulfasalazine, injectable gold, methotrexate, leflunomide, cyclosporine, or a thiopurine derivative (azathioprine or 6-mercaptopurine)

Exclusion Criteria:

• Current Therapy With Any DMARD Or Biologic

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 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: Belgium, Brazil, Canada, Germany, Italy, Mexico, Slovakia, Spain, United States
• Removed Location Countries: Austria

Administrative Information

• NCT Number: NCT00147498
• Other Study ID Numbers: A3921019
• 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: December 2012