Back to resultsA Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CP-690,550 + methotrexate
Placebo + Methotrexate
Sponsored by
About this trial
This is an interventional basic science trial for Rheumatoid Arthritis
Eligibility 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 .
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CP-690,550 + methotrexate
Placebo + methotrexate
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Osteoprotegerin (OPG) Level at Pre-dose on Day 1
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1
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
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at Pre-dose on Day 10
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Osteoprotegerin (OPG) Level at Pre-dose on Day 28
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
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
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
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
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
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Plasma Level of Matrix Metallopeptidase (MMP13)
Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
Secondary Outcome Measures
Percentage of Participants Achieving American College of Rheumatology 20% Response
ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
ACR50 response: >=50% improvement in TJC; >= 50% improvement in SJC; and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
ACR70 response: >=70% improvement in TJC; >= 70% improvement in SJC; and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP) (milligram per liter [mg/L]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity, greater than (>) 3.2 to 5.1 implied moderate to high disease activity and less than (<) 2.6 implied remission.
Change From Baseline in Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Day 28 and 35
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Percentage of Participants With Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) <=3.2 and <2.6
DAS28-3 (CRP) was calculated from the SJC, TJC using the 28 joints count and the CRP (mg/mL). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Change From Baseline in Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Day 28 and 35
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR [mm/hour] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) <=3.2 and <2.6
DAS28-4 (ESR) was calculated from the number of SJC, TJC using the 28 joints count, ESR [mm/hour] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity, > 3.2 to 5.1 implied moderate to high disease activity and <2.6 implied remission.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00976599
Brief Title
A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CP-690,550 + methotrexate
Arm Type
Experimental
Arm Title
Placebo + methotrexate
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
CP-690,550 + methotrexate
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo + Methotrexate
Intervention Description
Methotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week
Primary Outcome Measure Information:
Title
Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28
Description
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.
Time Frame
Day -7 (Baseline), Day 28
Title
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
Description
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.
Time Frame
Baseline (Day -7), Day 28
Title
Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28
Description
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.
Time Frame
Baseline (Day -7), Day 28
Title
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)
Description
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.
Time Frame
Baseline (Day -7)
Title
Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28
Description
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.
Time Frame
Day 28
Title
Blood Cytokine Level at Pre-dose on Day 1
Description
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).
Time Frame
Pre-dose on Day 1
Title
Blood Cytokine Level at 1 Hour Post-dose on Day 1
Description
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.
Time Frame
1 hour post-dose on Day 1
Title
Blood Cytokine Level at 4 Hours Post-dose on Day 1
Description
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.
Time Frame
4 hours post-dose on Day 1
Title
Blood Cytokine Level at Pre-dose on Day 10
Description
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.
Time Frame
Pre-dose on Day 10
Title
Blood Cytokine Level at Pre-dose on Day 28
Description
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.
Time Frame
Pre-dose on Day 28
Title
Blood Cytokine Level at 1 Hour Post-dose on Day 28
Description
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.
Time Frame
1 Hour Post-dose on Day 28
Title
Blood Cytokine Level at 4 Hours Post-dose on Day 28
Description
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.
Time Frame
4 Hours Post-dose on Day 28
Title
Blood Cytokine Level at 8 Hours Post-dose on Day 28
Description
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.
Time Frame
8 Hours Post-dose on Day 28
Title
Blood Cytokine Level at 24 Hours Post-dose on Day 28
Description
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.
Time Frame
24 Hours Post-dose on Day 28
Title
Blood Cytokine Level at Pre-dose on Day 35 or Early Termination
Description
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.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1
Description
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.
Time Frame
Pre-dose on Day 1
Title
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1
Description
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.
Time Frame
1 Hour Post-dose on Day 1
Title
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1
Description
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.
Time Frame
4 Hours Post-dose on Day 1
Title
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10
Description
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.
Time Frame
Pre-dose on Day 10
Title
Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28
Description
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.
Time Frame
Pre-dose on Day 28
Title
Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28
Description
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.
Time Frame
1 Hour Post-dose on Day 28
Title
Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28
Description
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.
Time Frame
4 Hours Post-dose on Day 28
Title
Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28
Description
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.
Time Frame
8 Hours Post-dose on Day 28
Title
Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28
Description
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.
Time Frame
24 Hours Post-dose on Day 28
Title
Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination
Description
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.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1
Description
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).
Time Frame
Pre-dose on Day 1
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1
Description
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.
Time Frame
1 Hour Post-dose on Day 1
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1
Description
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.
Time Frame
4 Hours Post-dose on Day 1
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10
Description
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.
Time Frame
Pre-dose on Day 10
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28
Description
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.
Time Frame
Pre-dose on Day 28
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28
Description
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.
Time Frame
1 Hour Post-dose on Day 28
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28
Description
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.
Time Frame
4 Hours Post-dose on Day 28
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28
Description
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.
Time Frame
8 Hours Post-dose on Day 28
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28
Description
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.
Time Frame
24 Hours Post-dose on Day 28
Title
Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination
Description
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.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Parathyroid Hormone (PTH) Level at Pre-dose on Day 1
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
Pre-dose on Day 1
Title
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
1 Hour Post-dose on Day 1
Title
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
4 Hours Post-dose on Day 1
Title
Parathyroid Hormone (PTH) Level at Pre-dose on Day 10
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
Pre-dose on Day 10
Title
Parathyroid Hormone (PTH) Level at Pre-dose on Day 28
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
Pre-dose on Day 28
Title
Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
1 Hour Post-dose on Day 28
Title
Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
4 Hours Post-dose on Day 28
Title
Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
8 Hours Post-dose on Day 28
Title
Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
24 Hours Post-dose on Day 28
Title
Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination
Description
Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Osteoprotegerin (OPG) Level at Pre-dose on Day 1
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 1
Title
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
1 Hour Post-dose on Day 1
Title
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
4 Hours Post-dose on Day 1
Title
Osteoprotegerin (OPG) Level at Pre-dose on Day 10
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 10
Title
Osteoprotegerin (OPG) Level at Pre-dose on Day 28
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 28
Title
Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
1 Hour Post-dose on Day 28
Title
Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
4 Hours Post-dose on Day 28
Title
Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
8 Hours Post-dose on Day 28
Title
Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
24 Hours Post-dose on Day 28
Title
Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination
Description
Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
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
Title
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
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1
Description
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).
Time Frame
Pre-dose on Day 1
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1
Description
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.
Time Frame
1 Hour Post-dose on Day 1
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1
Description
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.
Time Frame
4 Hours Post-dose on Day 1
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10
Description
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.
Time Frame
Pre-dose on Day 10
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28
Description
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.
Time Frame
Pre-dose on Day 28
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28
Description
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.
Time Frame
1 Hour Post-dose on Day 28
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28
Description
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.
Time Frame
4 Hours Post-dose on Day 28
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28
Description
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.
Time Frame
8 Hours Post-dose on Day 28
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28
Description
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.
Time Frame
24 Hours Post-dose on Day 28
Title
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination
Description
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.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 1
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
1 Hour Post-dose on Day 1
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
4 Hours Post-dose on Day 1
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 10
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 28
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
1 Hour Post-dose on Day 28
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
4 Hours Post-dose on Day 28
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
8 Hours Post-dose on Day 28
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
24 Hours Post-dose on Day 28
Title
Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination
Description
Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.
Time Frame
Pre-dose on Day 35 or Early Termination
Title
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1
Description
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).
Time Frame
Pre-dose on Day 1
Title
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10
Description
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Time Frame
Pre-dose on Day 10
Title
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28
Description
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Time Frame
Pre-dose on Day 28
Title
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28
Description
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Time Frame
24 Hours Post-dose on Day 28
Title
Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination
Description
Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.
Time Frame
Pre-dose on Day 35 or Early Termination
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving American College of Rheumatology 20% Response
Description
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).
Time Frame
Day 28, 35 or Early Termination
Title
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Description
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.
Time Frame
Day 28, 35 or Early Termination
Title
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Description
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.
Time Frame
Day 28, 35 or Early Termination
Title
Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Description
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.
Time Frame
Day -7, 1 (Baseline), 28, 35 or Early Termination
Title
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
Description
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.
Time Frame
Day 1 (Baseline), 28, 35 or Early Termination
Title
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
Description
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.
Time Frame
Day -7, 1 (Baseline), 28, 35 or Early Termination
Title
Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Description
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.
Time Frame
Day -7, 1 (Baseline), 28, 35 or Early Termination
Title
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
Description
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.
Time Frame
Day 1 (Baseline), 28, 35 or Early Termination
Title
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
Description
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.
Time Frame
Day -7, 1 (Baseline), 28, 35 or Early Termination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 .
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
Pfizer Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Pfizer Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Facility Name
Pfizer Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Pfizer Investigational Site
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21702
Country
United States
Facility Name
Pfizer Investigational Site
City
Battle Creek
State/Province
Michigan
ZIP/Postal Code
49015
Country
United States
Facility Name
Pfizer Investigational Site
City
Mayfield Village
State/Province
Ohio
ZIP/Postal Code
44143
Country
United States
Facility Name
Pfizer Investigational Site
City
Mentor
State/Province
Ohio
ZIP/Postal Code
44060
Country
United States
Facility Name
Pfizer Investigational Site
City
Willoughby
State/Province
Ohio
ZIP/Postal Code
44094
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
Facility Name
Pfizer Investigational Site
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Pfizer Investigational Site
City
Sunnyvale
State/Province
Texas
ZIP/Postal Code
75182
Country
United States
Facility Name
Pfizer Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Pfizer Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34870800
Citation
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.
Results Reference
derived
PubMed Identifier
33127856
Citation
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.
Results Reference
derived
PubMed Identifier
32816215
Citation
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. Erratum In: Dig Dis Sci. 2020 Oct 10;:
Results Reference
derived
PubMed Identifier
28143815
Citation
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.
Results Reference
derived
PubMed Identifier
25398374
Citation
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.
Results Reference
derived
PubMed Identifier
25047021
Citation
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921073&StudyName=A%20Study%20To%20Evaluate%20The%20Mechanism%20Of%20Action%20Of%20CP-690%2C550%20In%20Patients%20With%20Rheumatoid%20Arthritis
Description
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Learn more about this trial
A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis
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