Rheumatoid ArthritisPhase 2NCT00976599

A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis

A Phase 2 study testing CP-690,550 + methotrexate in people with Rheumatoid Arthritis, run by Pfizer at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: CP-690,550 + methotrexate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 15 sitesUnited States
Study dates: Nov 2009to Jul 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subject must have a diagnosis of rheumatoid arthritis based on the American College of Rheumatology Association
The subject has active disease at both Screening and Baseline, as defined:
≥4 joints tender or painful on motion, AND
≥4 joints swollen;
The subject must have at least one knee, one elbow, one wrist or two metacarpophalangeal joints with active synovitis suitable for biopsy by the shaver technique

Who cannot join

No arthroscopy should have been performed in the past 3 months in the same joint that is to be biopsied in this study.
No intra-articular steroids should have been injected in the joint to be biopsied in this study in the previous 3 months.
Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels < 9.0 gm/dL or hematocrit < 30 % at screening visit or within the 3 months prior to baseline synovial biopsy.
An absolute white blood cell (WBC) count of < 3.0 x 109/L (<3000/mm3) or absolute neutrophil count of <1.2 X 109/L (<1200/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
Thrombocytopenia, as defined by a platelet count <100 x 109/L (< 100,000/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
Estimated GFR less than 40 ml/min based on Cockcroft Gault calculation .

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

United States15 sites

Pfizer Investigational Site
Battle Creek, Michigan, 49015
Pfizer Investigational Site
Birmingham, Alabama, 35205
Pfizer Investigational Site
Birmingham, Alabama, 35209
Pfizer Investigational Site
Birmingham, Alabama, 35216
Pfizer Investigational Site
Dallas, Texas, 75231
Pfizer Investigational Site
Dallas, Texas, 75251
Pfizer Investigational Site
Frederick, Maryland, 21702
Pfizer Investigational Site
La Jolla, California, 92037
Pfizer Investigational Site
Mayfield Village, Ohio, 44143
Pfizer Investigational Site
Mentor, Ohio, 44060
Pfizer Investigational Site
Mesquite, Texas, 75150
Pfizer Investigational Site
Seattle, Washington, 98104
Pfizer Investigational Site
Seattle, Washington, 98122
Pfizer Investigational Site
Sunnyvale, Texas, 75182
Pfizer Investigational Site
Willoughby, Ohio, 44094

Other trials in United States

About this study

Official title: 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

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.

Conditions: Rheumatoid Arthritis
Being tested: CP-690,550 + methotrexate, Placebo + Methotrexate
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CP-690,550 + methotrexateDrug
CP-690,550 dose is 10 mg twice daily, oral tablets, for 4 weeks Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week
Placebo + MethotrexateDrug
Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week

Study groups in NCT00976599
Study group	Role	What they receive
CP-690,550 + methotrexate	Experimental	Not described Receives: Drug: CP-690,550 + methotrexate
Placebo + methotrexate	Placebo comparator	Not described Receives: Drug: Placebo + Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at 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 (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.
Measured: Day -7 (Baseline), Day 28
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
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.
Measured: Baseline (Day -7), Day 28
Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at 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.
Measured: Baseline (Day -7), Day 28
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at 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 expression (relative expression) within blood.
Measured: Baseline (Day -7)
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at 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 (relative expression) within blood.
Measured: Day 28
Blood Cytokine Level at 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 inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).
Measured: Pre-dose on Day 1
Blood Cytokine Level at 1 Hour Post-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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 1 hour post-dose on Day 1
Blood Cytokine Level at 4 Hours Post-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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 4 hours post-dose on Day 1
Blood Cytokine Level at Pre-dose on Day 10
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: Pre-dose on Day 10
Blood Cytokine Level at Pre-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: Pre-dose on Day 28
Blood Cytokine Level at 1 Hour Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 1 Hour Post-dose on Day 28
Blood Cytokine Level at 4 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 4 Hours Post-dose on Day 28
Blood Cytokine Level at 8 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 8 Hours Post-dose on Day 28
Blood Cytokine Level at 24 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: 24 Hours Post-dose on Day 28
Blood Cytokine Level at Pre-dose on Day 35 or Early Termination
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Measured: Pre-dose on Day 35 or Early Termination
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1
Blood samples were collected for fluorescence-activated cell sorting [FACS] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.
Measured: Pre-dose on Day 1
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 1 Hour Post-dose on Day 1
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 4 Hours Post-dose on Day 1
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: Pre-dose on Day 10
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: Pre-dose on Day 28
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 1 Hour Post-dose on Day 28
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 4 Hours Post-dose on Day 28
Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 8 Hours Post-dose on Day 28
Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: 24 Hours Post-dose on Day 28
Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Measured: Pre-dose on Day 35 or Early Termination
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay [ELISA] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).
Measured: Pre-dose on Day 1
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 1 Hour Post-dose on Day 1
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 4 Hours Post-dose on Day 1
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: Pre-dose on Day 10
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: Pre-dose on Day 28
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 1 Hour Post-dose on Day 28
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 4 Hours Post-dose on Day 28
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 8 Hours Post-dose on Day 28
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: 24 Hours Post-dose on Day 28
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Measured: Pre-dose on Day 35 or Early Termination
Parathyroid Hormone (PTH) Level at Pre-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: Pre-dose on Day 1
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 1 Hour Post-dose on Day 1
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 4 Hours Post-dose on Day 1
Parathyroid Hormone (PTH) Level at Pre-dose on Day 10
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: Pre-dose on Day 10
Parathyroid Hormone (PTH) Level at Pre-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: Pre-dose on Day 28
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 1 Hour Post-dose on Day 28
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 4 Hours Post-dose on Day 28
Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 8 Hours Post-dose on Day 28
Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: 24 Hours Post-dose on Day 28
Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Measured: Pre-dose on Day 35 or Early Termination
Osteoprotegerin (OPG) Level at Pre-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 1
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 1 Hour Post-dose on Day 1
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 4 Hours Post-dose on Day 1
Osteoprotegerin (OPG) Level at Pre-dose on Day 10
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 10
Osteoprotegerin (OPG) Level at Pre-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 28
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 1 Hour Post-dose on Day 28
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 4 Hours Post-dose on Day 28
Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 8 Hours Post-dose on Day 28
Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: 24 Hours Post-dose on Day 28
Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 35 or Early Termination
Plasma Level of Matrix Metallopeptidase (MMP13)
Measured: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)
Measured: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1
Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).
Measured: Pre-dose on Day 1
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 1 Hour Post-dose on Day 1
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 4 Hours Post-dose on Day 1
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: Pre-dose on Day 10
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: Pre-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 1 Hour Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 4 Hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 8 Hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: 24 Hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Measured: Pre-dose on Day 35 or Early Termination
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 1
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 1 Hour Post-dose on Day 1
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 4 Hours Post-dose on Day 1
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 10
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 28
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 1 Hour Post-dose on Day 28
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 4 Hours Post-dose on Day 28
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 8 Hours Post-dose on Day 28
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: 24 Hours Post-dose on Day 28
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Measured: Pre-dose on Day 35 or Early Termination
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).
Measured: Pre-dose on Day 1
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Measured: Pre-dose on Day 10
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Measured: Pre-dose on Day 28
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Measured: 24 Hours Post-dose on Day 28
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Measured: Pre-dose on Day 35 or Early Termination

Secondary outcomes (9)

Percentage of Participants Achieving American College of Rheumatology 20% Response
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).
Measured: Day 28, 35 or Early Termination
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 response: >=50% improvement in TJC; >= 50% improvement in 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.
Measured: Day 28, 35 or Early Termination
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response: >=70% improvement in TJC; >= 70% improvement in 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.
Measured: Day 28, 35 or Early Termination
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP) (milligram per liter [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, greater than (>) 3.2 to 5.1 implied moderate to high disease activity and less than (<) 2.6 implied remission.
Measured: Day -7, 1 (Baseline), 28, 35 or Early Termination
Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 28 and 35
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Measured: Day 1 (Baseline), 28, 35 or Early Termination
Percentage of Participants With Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) <=3.2 and <2.6
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Measured: Day -7, 1 (Baseline), 28, 35 or Early Termination
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores 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 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Measured: Day -7, 1 (Baseline), 28, 35 or Early Termination
Change From Baseline in Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Day 28 and 35
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR [mm/hour] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores 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 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Measured: Day 1 (Baseline), 28, 35 or Early Termination
Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) <=3.2 and <2.6
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR [mm/hour] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores 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 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Measured: Day -7, 1 (Baseline), 28, 35 or Early Termination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Jul 2011

First posted14 Sep 2009 (estimated)
Study startNov 2009
Primary completionJul 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00976599
Sponsor's protocol ID: A3921073
Status last verified: Dec 2012
First submitted: 11 Sep 2009
Last updated: 9 Jan 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Wright G, Mysler E, Roberts KD, Shelbaya A, Sweet L, Masri KR. Impact of the Sociodemographic Index on Efficacy/Safety of Tofacitinib in Patients with Rheumatoid Arthritis: Post Hoc Analysis of Phase 2/3/3b/4 Studies. Rheumatol Ther. 2026 Oct 16. doi: 10.1007/s40744-026-00881-y. Online ahead of print.
PubMed 42888330
Hetland ML, Strangfeld A, Bonfanti G, Soudis D, Deuring JJ, Edwards RA. Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib. Arthritis Res Ther. 2024 Aug 27;26(1):153. doi: 10.1186/s13075-024-03376-9.
PubMed 39192350
Wright GC, Mysler E, Kwok K, Cadatal MJ, Germino R, Yndestad A, Kinch CD, Ogdie A. Impact of Race on the Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis: Post Hoc Analysis of Pooled Clinical Trials. Rheumatol Ther. 2024 Oct;11(5):1135-1164. doi: 10.1007/s40744-024-00677-y. Epub 2024 Jul 3.
PubMed 38958913
Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.
PubMed 36931693
Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.
PubMed 36601090
Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.
PubMed 36600185
Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.
PubMed 36526796
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.
PubMed 34870800
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.
PubMed 33127856
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.
PubMed 32816215
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.
PubMed 28143815
Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6):1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.
PubMed 25398374
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.
PubMed 25047021

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Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Study at a glance

From the registry record, last updated by the sponsor on 9 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT00976599
Acronym / sponsor ID: A3921073
Conditions: Rheumatoid Arthritis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Nov 2009
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 14 Sep 2009 (estimated)
Results: Posted 9 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CP-690,550 + methotrexate	Experimental	Drug: CP-690,550 + methotrexate
Placebo + methotrexate	Placebo comparator	Drug: Placebo + Methotrexate

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Subject must have a diagnosis of rheumatoid arthritis based on the American College of Rheumatology Association
The subject has active disease at both Screening and Baseline, as defined:
The subject must have at least one knee, one elbow, one wrist or two metacarpophalangeal joints with active synovitis suitable for biopsy by the shaver technique

Key exclusion criteria (6 listed)

No arthroscopy should have been performed in the past 3 months in the same joint that is to be biopsied in this study.
No intra-articular steroids should have been injected in the joint to be biopsied in this study in the previous 3 months.
Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels < 9.0 gm/dL or hematocrit < 30 % at screening visit or within the 3 months prior to baseline synovial biopsy.
An absolute white blood cell (WBC) count of < 3.0 x 109/L (<3000/mm3) or absolute neutrophil count of <1.2 X 109/L (<1200/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
Thrombocytopenia, as defined by a platelet count <100 x 109/L (< 100,000/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CP-690,550 + methotrexateCP-690,550 dose is 10 mg twice daily, oral tablets, for 4 weeks Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week	Drug	CP-690,550 + methotrexate
Placebo + MethotrexateMethotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week	Drug	Placebo + methotrexate

Primary outcome

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 (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.
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 expression (relative expression) within blood.
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 (relative expression) within blood.
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 inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).
Blood Cytokine Level at 1 Hour Post-dose on Day 1
Time frame: 1 hour post-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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at 4 Hours Post-dose on Day 1
Time frame: 4 hours post-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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood Cytokine Level at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
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, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Blood samples were collected for fluorescence-activated cell sorting [FACS] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay [ELISA] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.
Parathyroid Hormone (PTH) Level at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Osteoprotegerin (OPG) Level at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Plasma Level of Matrix Metallopeptidase (MMP13)
Time frame: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)
Time frame: Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1
Time frame: 1 Hour Post-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1
Time frame: 4 Hours Post-dose on Day 1
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28
Time frame: 1 Hour Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28
Time frame: 4 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28
Time frame: 8 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1
Time frame: Pre-dose on Day 1
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10
Time frame: Pre-dose on Day 10
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28
Time frame: Pre-dose on Day 28
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28
Time frame: 24 Hours Post-dose on Day 28
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination
Time frame: Pre-dose on Day 35 or Early Termination
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

9 secondary outcomes

Percentage of Participants Achieving American College of Rheumatology 20% Response
Time frame: Day 28, 35 or Early Termination
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Time frame: Day 28, 35 or Early Termination
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Time frame: Day 28, 35 or Early Termination
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination
Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 28 and 35
Time frame: Day 1 (Baseline), 28, 35 or Early Termination
Percentage of Participants With Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) <=3.2 and <2.6
Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination
Change From Baseline in Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Day 28 and 35
Time frame: Day 1 (Baseline), 28, 35 or Early Termination
Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) <=3.2 and <2.6
Time frame: Day -7, 1 (Baseline), 28, 35 or Early Termination

Results and safety

Results posted to the registry on 9 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CP-690,550	15	15
Placebo	14	14

Primary outcome: Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28

Time frame: Day -7 (Baseline), Day 28. Mean (Standard Deviation). Unit: relative expression unit (REU)

Measure	CP-690,550 n = 15	Placebo n = 14
Baseline: IL-1beta mRNA	-2.73 (0.77)	-2.83 (0.80)
Baseline: IL-6 mRNA	-3.72 (0.67)	-3.96 (0.55)
Baseline: MMP3 mRNA	-2.01 (1.39)	-2.52 (1.64)
Baseline: CD19 mRNA	-2.98 (1.25)	-3.46 (1.34)
Baseline: CD3E mRNA	-1.58 (0.71)	-1.75 (0.58)
Baseline: JAK1 mRNA	0.30 (0.24)	0.31 (0.29)
Baseline: JAK2 mRNA	0.17 (0.26)	0.15 (0.25)
Baseline: JAK3 mRNA	-0.77 (0.40)	-0.88 (0.52)

Population analysed: Full analysis set (FAS) included all randomized participants who received at least 1 dose of the study medication. Analyses of tumor necrosis factor alpha(TNFα), receptor activator of nuclear factor kappa-B ligand(RANKL), osteoprotegerin(OPG) were not performed due to insufficient samples and lack of appropriate method to process/analyze samples.

Primary outcome: 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

Population analysed: Analyses of TNFalpha, IL-6, IL-17 and IL-10 were not performed due to insufficient samples and lack of appropriate method to process/analyze the samples.

Primary outcome: 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. Mean (Standard Deviation). Unit: percentage area stained

Measure	CP-690,550 n = 12	Placebo n = 12
Baseline: CD3+ Cells (n=12, 12)	7.33 (6.12)	7.92 (7.49)
Baseline: CD68+ Cells (n=12, 13)	31.83 (20.59)	32.85 (26.05)
Change at Day 28: CD3+ Cells (n=10, 8)	1.50 (3.95)	0.13 (7.38)
Change at Day 28: CD68+ Cells (n=12, 11)	1.67 (19.86)	0.82 (18.37)

Population analysed: FAS included all randomized participants who received at least 1 dose of the study medication. Here, 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure. n=number of participants evaluable at specific time points for each arm group, respectively.

Primary outcome: Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)

Time frame: Baseline (Day -7). Mean (Standard Deviation). Unit: REU

Measure	CP-690,550 n = 14	Placebo n = 14
CD19 mRNA	0.11 (0.28)	0.29 (0.25)
CD3E mRNA	0.41 (0.44)	0.40 (0.38)
STAT1 mRNA	0.06 (0.25)	0.02 (0.13)
STAT3 mRNA	0.61 (0.13)	0.64 (0.08)
ISG15 mRNA	-0.65 (0.45)	-0.56 (0.47)
CXCL10 mRNA	-1.58 (0.33)	-1.65 (0.19)

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CP-690,550	0 of 15 (0%)	7 of 15 (46.7%)	Not reported
Placebo	0 of 14 (0%)	10 of 14 (71.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42888330Wright G, Mysler E, Roberts KD, Shelbaya A, Sweet L, Masri KR. Impact of the Sociodemographic Index on Efficacy/Safety of Tofacitinib in Patients with Rheumatoid Arthritis: Post Hoc Analysis of Phase 2/3/3b/4 Studies. Rheumatol Ther. 2026 Oct 16. doi: 10.1007/s40744-026-00881-y. Online ahead of print.
Derived from this study: PubMed 39192350Hetland ML, Strangfeld A, Bonfanti G, Soudis D, Deuring JJ, Edwards RA. Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib. Arthritis Res Ther. 2024 Aug 27;26(1):153. doi: 10.1186/s13075-024-03376-9.
Derived from this study: PubMed 38958913Wright GC, Mysler E, Kwok K, Cadatal MJ, Germino R, Yndestad A, Kinch CD, Ogdie A. Impact of Race on the Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis: Post Hoc Analysis of Pooled Clinical Trials. Rheumatol Ther. 2024 Oct;11(5):1135-1164. doi: 10.1007/s40744-024-00677-y. Epub 2024 Jul 3.
Derived from this study: PubMed 36931693Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.
Derived from this study: PubMed 36601090Hansen KE, Mortezavi M, Nagy E, Wang C, Connell CA, Radi Z, Litman HJ, Adami G, Rossini M. Fracture in clinical studies of tofacitinib in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022 Dec 27;14:1759720X221142346. doi: 10.1177/1759720X221142346. eCollection 2022.
Derived from this study: PubMed 36600185Curtis JR, Yamaoka K, Chen YH, Bhatt DL, Gunay LM, Sugiyama N, Connell CA, Wang C, Wu J, Menon S, Vranic I, Gomez-Reino JJ. Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomised controlled ORAL Surveillance trial. Ann Rheum Dis. 2023 Mar;82(3):331-343. doi: 10.1136/ard-2022-222543. Epub 2022 Dec 5.
Derived from this study: PubMed 36526796Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.
Derived from this study: PubMed 34870800Winthrop 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.
Derived from this study: PubMed 33127856Cohen 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.
Derived from this study: PubMed 32816215Panaccione 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.
Derived from this study: PubMed 28143815Cohen 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.
Derived from this study: PubMed 25398374Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6):1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.
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Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CP-690,550 + methotrexate in people with Rheumatoid Arthritis, run by Pfizer at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 (time frame: Day -7 (Baseline), Day 28). The study lists 82 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00976599, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2013.