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

NCT00976599 | Completed Phase 2 Results

• 1 other identifier: A3921073
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (82)

• 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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Pre-dose on Day 35 or Early Termination

• Plasma Level of Matrix Metallopeptidase (MMP13)

  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)

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  Pre-dose on Day 35 or Early Termination

Secondary Outcomes (9)

• Percentage of Participants Achieving American College of Rheumatology 20% Response

  Day 28, 35 or Early Termination

• Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response

  Day 28, 35 or Early Termination

• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

  Day 28, 35 or Early Termination

• Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])

  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

  Day 1 (Baseline), 28, 35 or Early Termination

Study Arms (2)

CP-690,550 + methotrexate

EXPERIMENTAL

Drug: CP-690,550 + methotrexate

Placebo + methotrexate

PLACEBO COMPARATOR

Drug: Placebo + Methotrexate

Interventions

CP-690,550 + methotrexate DRUG

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

CP-690,550 + methotrexate

Placebo + Methotrexate DRUG

Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week

Placebo + methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Pfizer: lead

Study Sites (15)

Pfizer Investigational Site

Birmingham, Alabama, 35205, United States

Location

Pfizer Investigational Site

Birmingham, Alabama, 35209, United States

Location

Pfizer Investigational Site

Birmingham, Alabama, 35216, United States

Location

Pfizer Investigational Site

La Jolla, California, 92037, United States

Location

Pfizer Investigational Site

Frederick, Maryland, 21702, United States

Location

Pfizer Investigational Site

Battle Creek, Michigan, 49015, United States

Location

Pfizer Investigational Site

Mayfield Village, Ohio, 44143, United States

Location

Pfizer Investigational Site

Mentor, Ohio, 44060, United States

Location

Pfizer Investigational Site

Willoughby, Ohio, 44094, United States

Location

Pfizer Investigational Site

Dallas, Texas, 75231, United States

Location

Pfizer Investigational Site

Dallas, Texas, 75251, United States

Location

Pfizer Investigational Site

Mesquite, Texas, 75150, United States

Location

Pfizer Investigational Site

Sunnyvale, Texas, 75182, United States

Location

Pfizer Investigational Site

Seattle, Washington, 98104, United States

Location

Pfizer Investigational Site

Seattle, Washington, 98122, United States

Location

Related Publications (12)

• 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.

  PMID: 39192350 DERIVED

• 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.

  PMID: 38958913 DERIVED

• 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.

  PMID: 36931693 DERIVED

• 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.

  PMID: 36601090 DERIVED

• 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.

  PMID: 36600185 DERIVED

• 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.

  PMID: 36526796 DERIVED

• 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.

  PMID: 34870800 DERIVED

• 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.

  PMID: 33127856 DERIVED

• 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.

  PMID: 32816215 DERIVED

• 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.

  PMID: 28143815 DERIVED

• 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.

  PMID: 25398374 DERIVED

• 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.

  PMID: 25047021 DERIVED

Related Links

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

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: November 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: January 9, 2013
• Results First Posted: January 9, 2013

Record last verified: 2012-12

Locations

US (15)