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

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

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Placebo; Drug: CP-690,550; Drug: CP-690,550; Drug: CP-690,550

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Pfizer Investigational Site
• Brazil
  • GO
    • Goiânia, GO, Brazil, 74043-110
      • Pfizer Investigational Site
    • Goiânia, GO, Brazil, 74110-120
      • Pfizer Investigational Site
  • PR
    • Curitiba, PR, Brazil, 80060-240
      • Pfizer Investigational Site
  • SP
    • São Paulo, SP, Brazil, 04230-000
      • Pfizer Investigational Site
    • São Paulo, SP, Brazil, 05001-000
      • Pfizer Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
      • Pfizer Investigational Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8P 5P6
      • Pfizer Investigational Site
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1C 5B8
      • Pfizer Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10098
    • Pfizer Investigational Site
  • Dresden, Germany, 01067
    • Pfizer Investigational Site
  • Hamburg, Germany, 22081
    • Pfizer Investigational Site
  • Hildesheim, Germany, 31134
    • Pfizer Investigational Site
  • Leipzig, Germany, 04103
    • Pfizer Investigational Site
  • Muenchen, Germany, 80639
    • Pfizer Investigational Site
  • Neubrandenburg, Germany, 17033
    • Pfizer Investigational Site
  • Wiesbaden, Germany, 65191
    • Pfizer Investigational Site
• Italy
  • Firenze, Italy, 50139
    • Pfizer Investigational Site
  • Genova, Italy, 16132
    • Pfizer Investigational Site
  • Pavia, Italy, 27100
    • Pfizer Investigational Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Pfizer Investigational Site
  • San Luis Potosí, Mexico, 78240
    • Pfizer Investigational Site
  • D.f.
    • México, D.f., Mexico, 06726
      • Pfizer Investigational Site
  • DF
    • Tlalpan Seccion 16, DF, Mexico, 14000
      • Pfizer Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44690
      • Pfizer Investigational Site
• Slovakia
  • Kosice, Slovakia, 040 11
    • Pfizer Investigational Site
  • Piestany, Slovakia, 921 01
    • Pfizer Investigational Site
  • Zilina, Slovakia, 012 07
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08003
    • Pfizer Investigational Site
  • Guadalajara, Spain, 19002
    • Pfizer Investigational Site
  • Madrid, Spain, 28046
    • Pfizer Investigational Site
  • Sevilla, Spain, 41014
    • Pfizer Investigational Site
  • Barcelona
    • L´hospitalet de Llobregat, Barcelona, Spain, 08907
      • Pfizer Investigational Site
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Pfizer Investigational Site
• United States
  • California
    • Upland, California, United States, 91786
      • Pfizer Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33173
      • Pfizer Investigational Site
    • New Port Richey, Florida, United States, 34652
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34474-7455
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32804
      • Pfizer Investigational Site
    • Port Richey, Florida, United States, 34668
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33614
      • Pfizer Investigational Site
  • Iowa
    • Dubuque, Iowa, United States, 52002
      • Pfizer Investigational Site
    • Dubuque, Iowa, United States, 52001-7313
      • Pfizer Investigational Site
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Pfizer Investigational Site
  • New York
    • Plainview, New York, United States, 11803
      • Pfizer Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Pfizer Investigational Site
    • Hickory, North Carolina, United States, 28601
      • Pfizer Investigational Site
    • Hickory, North Carolina, United States, 28602
      • Pfizer Investigational Site
  • Ohio
    • Dayton, Ohio, United States, 45402
      • Pfizer Investigational Site
  • Pennsylvania
    • Ducansville, Pennsylvania, United States, 16635
      • Pfizer Investigational Site
    • Johnstown, Pennsylvania, United States, 15904
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Pfizer Investigational Site
    • Columbia, South Carolina, United States, 29204
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75231-4496
      • Pfizer Investigational Site
  • Washington
    • Everett, Washington, United States, 98201
      • Pfizer Investigational Site
    • Tacoma, Washington, United States, 98405
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo tablets
Experimental: 5 mg BID; CP 690,550 5 mg BID	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
Experimental: 15 mg BID; CP 690,550 15 mg BID	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
Experimental: 30 mg BID; Oral tablets administered at a dose of 30 mg BID for 6 weeks	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 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).	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	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.	Week 1, 2, 4, and 8
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	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.	Week 1, 2, 4, 6, and 8
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	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.	Week 1, 2, 4, 6, and 8
Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve	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.	Baseline up to Week 6
Tender Joints Count (TJC)	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Tender Joints Count (TJC) at 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.	Baseline, Week 1, 2, 4, 6, and 8
Swollen Joints Count (SJC)	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Swollen Joints Count (SJC) at 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.	Baseline, Week 1, 2, 4, 6, and 8
Patient Global Assessment (PtGA) of Arthritis	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at 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.	Baseline, Week 1, 2, 4, 6, and 8
Physician Global Assessment of Arthritis	Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Physician Global Assessment of Arthritis at 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.	Baseline, Week 1, 2, 4, 6, and 8
Patient Assessment of Arthritis Pain	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Patient Assessment of Arthritis Pain at 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.	Baseline, Week 1, 2, 4, 6, and 8
Health Assessment Questionnaire-Disability Index (HAQ-DI)	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at 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.	Baseline, Week 1, 2, 4, 6, and 8
C-Reactive Protein (CRP)	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.	Baseline, Week 1, 2, 4, 6, and 8
Change From Baseline in C-Reactive Protein (CRP) at 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.	Baseline, Week 1, 2, 4, 6, and 8
Disease Activity Score Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])	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.	Baseline, Week 1, 2, 4, 6, and 8
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	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.	Baseline, Week 1, 2, 4, 6, and 8
Number of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP)	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.	Baseline, Week 1, 2, 4, 6, and 8

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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;:
• 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, 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.
• 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.
• 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.
• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 7, 2005

Study Record Updates

• Last Update Posted (Estimate): January 30, 2013
• Last Update Submitted That Met QC Criteria: December 20, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Immune System Diseases; clinical trial; Autoimmune Diseases; rheumatic diseases; DMARD; joint diseases; Antirheumatic Agents; oral JAK inhibitor; anti-Inflammatory agents
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921019