NCT00976599

An Exploratory Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess The Pharmacodynamics Of CP-690,550, Administered Orally Twice Daily (BID) For 4 Weeks, In Subjects With Active Rheumatoid Arthritis

Completed Phase 2 Results posted Last updated 4 December 2012

What this trial tests

Phase 2 trial testing CP-690,550 + methotrexate in Rheumatoid Arthritis in 29 participants. Completed in 1 July 2011.

Timeline

1 November 2009

Primary endpoint
1 July 2011

1 July 2011

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	29
Start date	1 November 2009
Primary completion	1 July 2011
Estimated completion	1 July 2011
Sites	15 locations across United States

Drugs / interventions tested

• CP-690,550 + methotrexate — full drug profile →
• Placebo + Methotrexate

Conditions studied

• Rheumatoid Arthritis — all drugs for Rheumatoid Arthritis →

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28
  Time frame: Day -7 (Baseline), Day 28
  Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD
• Change From Baseline in Protein Expression of Tumor Necrosis Factor Alpha (TNFalpha), Interleukin-6 (IL-6), Interleukin-17a (IL-17a) and Interleukin-10 (IL-10) at Day 28
  Time frame: Baseline (Day -7), Day 28
  Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.
• Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28
  Time frame: Baseline (Day -7), Day 28
  The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.
• Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)
  Time frame: Baseline (Day -7)
  Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3 epsilon (CD3E), STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized e
• Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28
  Time frame: Day 28
  Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3E, STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (rel
• Blood Cytokine Level at Pre-dose on Day 1
  Time frame: Pre-dose on Day 1
  Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, active 70 kDa (p70) form of IL-12(IL-12p70), interferon gamma (IFNgamma) - induced protein 10 (IP-10), TNFalpha, granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage inf

Sponsor's own description

To explore the effect of CP-690,550 on blood and synovial markers in subjects with rheumatoid arthritis. To evaluate the safety, tolerability and efficacy of CP-690,550.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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.
   Cohen SB, Tanaka Y, Mariette X, Curtis JR, et al · · 2017 · cited 289× · PMID 28143815 · DOI 10.1136/annrheumdis-2016-210457
2. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.
   Boyle DL, Soma K, Hodge J, Kavanaugh A, et al · · 2015 · cited 215× · PMID 25398374 · DOI 10.1136/annrheumdis-2014-206028
3. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme.
   Cohen SB, Tanaka Y, Mariette X, Curtis JR, et al · · 2020 · cited 135× · PMID 33127856 · DOI 10.1136/rmdopen-2020-001395
4. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme.
   Curtis JR, Lee EB, Kaplan IV, Kwok K, et al · · 2016 · cited 112× · PMID 25902789 · DOI 10.1136/annrheumdis-2014-205847
5. Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications.
   Zhao J, Guo S, Schrodi SJ, He D. · · 2021 · cited 105× · PMID 34899757 · DOI 10.3389/fimmu.2021.790122
6. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial.
   Curtis JR, Yamaoka K, Chen YH, Bhatt DL, et al · · 2023 · cited 103× · PMID 36600185 · DOI 10.1136/ard-2022-222543
7. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance.
   Kristensen LE, Danese S, Yndestad A, Wang C, et al · · 2023 · cited 89× · PMID 36931693 · DOI 10.1136/ard-2022-223715
8. New developments implicating IL-21 in autoimmune disease.
   Ren HM, Lukacher AE, Rahman ZSM, Olsen NJ. · · 2021 · cited 69× · PMID 34224936 · DOI 10.1016/j.jaut.2021.102689