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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00976599
First received: September 11, 2009
Last updated: December 4, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: CP-690,550 + methotrexate
Drug: Placebo + Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 [ Time Frame: Day -7 (Baseline), Day 28 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.


Secondary Outcome Measures:
  • Percentage of Participants Achieving American College of Rheumatology 20% Response [ Time Frame: Day 28, 35 or Early Termination ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Day 28, 35 or Early Termination ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Day 28, 35 or Early Termination ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 29
Study Start Date: November 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CP-690,550 + methotrexate Drug: CP-690,550 + methotrexate
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 Comparator: Placebo + methotrexate Drug: Placebo + Methotrexate
Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 .
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976599

Locations
United States, Alabama
Pfizer Investigational Site
Birmingham, Alabama, United States, 35205
Pfizer Investigational Site
Birmingham, Alabama, United States, 35209
Pfizer Investigational Site
Birmingham, Alabama, United States, 35216
United States, California
Pfizer Investigational Site
La Jolla, California, United States, 92037
United States, Maryland
Pfizer Investigational Site
Frederick, Maryland, United States, 21702
United States, Michigan
Pfizer Investigational Site
Battle Creek, Michigan, United States, 49015
United States, Ohio
Pfizer Investigational Site
Mayfield Village, Ohio, United States, 44143
Pfizer Investigational Site
Mentor, Ohio, United States, 44060
Pfizer Investigational Site
Willoughby, Ohio, United States, 44094
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75251
Pfizer Investigational Site
Dallas, Texas, United States, 75231
Pfizer Investigational Site
Mesquite, Texas, United States, 75150
Pfizer Investigational Site
Sunnyvale, Texas, United States, 75182
United States, Washington
Pfizer Investigational Site
Seattle, Washington, United States, 98104
Pfizer Investigational Site
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00976599     History of Changes
Other Study ID Numbers: A3921073
Study First Received: September 11, 2009
Results First Received: December 4, 2012
Last Updated: December 4, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Tofacitinib
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014