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OpenTrials
Completed

NCT Number: NCT00976599

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Pfizer Investigational Site, Birmingham, Alabama, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 .

Treatment and study plan

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

Placebo + Methotrexate

Drug

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

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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).

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. 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.

  38. 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.

  39. 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.

  40. 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.

  41. 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.

  42. 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.

  43. 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.

  44. 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.

  45. 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.

  46. 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.

  47. 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.

  48. 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.

  49. 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.

  50. 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.

  51. 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.

  52. 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.

  53. 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.

  54. 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.

  55. 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.

  56. 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

  57. 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

  58. 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).

  59. 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.

  60. 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.

  61. 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.

  62. 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.

  63. 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.

  64. 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.

  65. 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.

  66. 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.

  67. 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.

  68. 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.

  69. 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.

  70. 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.

  71. 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.

  72. 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.

  73. 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.

  74. 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.

  75. 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.

  76. 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.

  77. 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.

  78. 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).

  79. 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.

  80. 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.

  81. 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.

  82. 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.

Secondary outcomes

  1. Percentage of Participants Achieving American College of Rheumatology 20% Response

    Time frame: Day 28, 35 or Early Termination

    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).

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

    Time frame: Day 28, 35 or Early Termination

    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.

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

    Time frame: Day 28, 35 or Early Termination

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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.

  7. 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

    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.

  8. 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

    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.

  9. 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

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Sep 14, 2009
Registry last updated
Jan 9, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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