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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976599
• Other study ID #: A3921073
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2009
• Last updated: December 4, 2012
• Start date: November 2009
• Est. completion date: July 2011

Study information

• Verified date: December 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To explore the effect of CP-690,550 on blood and synovial markers in subjects with rheumatoid arthritis. To evaluate the safety, tolerability and efficacy of CP-690,550.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 .

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• CP-690,550 + methotrexate
CP-690,550 dose is 10 mg twice daily, oral tablets, for 4 weeks Methotrexate dose is = 7.5 mg / week and = 25 mg / week
• Placebo + Methotrexate
Methotrexate dose is = 7.5 mg / week and = 25 mg / week

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Battle Creek	Michigan
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Frederick	Maryland
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	Mayfield Village	Ohio
United States	Pfizer Investigational Site	Mentor	Ohio
United States	Pfizer Investigational Site	Mesquite	Texas
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Sunnyvale	Texas
United States	Pfizer Investigational Site	Willoughby	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28	Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.	Day -7 (Baseline), Day 28	No
Primary	Change From Baseline in Protein Expression of Tumor Necrosis Factor Alpha (TNFalpha), Interleukin-6 (IL-6), Interleukin-17a (IL-17a) and Interleukin-10 (IL-10) at Day 28	Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.	Baseline (Day -7), Day 28	No
Primary	Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28	The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.	Baseline (Day -7), Day 28	No
Primary	Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)	Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3 epsilon (CD3E), STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.	Baseline (Day -7)	No
Primary	Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28	Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3E, STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.	Day 28	No
Primary	Blood Cytokine Level at Pre-dose on Day 1	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, active 70 kDa (p70) form of IL-12(IL-12p70), interferon gamma (IFNgamma) - induced protein 10 (IP-10), TNFalpha, granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).	Pre-dose on Day 1	No
Primary	Blood Cytokine Level at 1 Hour Post-dose on Day 1	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	1 hour post-dose on Day 1	No
Primary	Blood Cytokine Level at 4 Hours Post-dose on Day 1	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	4 hours post-dose on Day 1	No
Primary	Blood Cytokine Level at Pre-dose on Day 10	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	Pre-dose on Day 10	No
Primary	Blood Cytokine Level at Pre-dose on Day 28	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	Pre-dose on Day 28	No
Primary	Blood Cytokine Level at 1 Hour Post-dose on Day 28	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	1 Hour Post-dose on Day 28	No
Primary	Blood Cytokine Level at 4 Hours Post-dose on Day 28	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	4 Hours Post-dose on Day 28	No
Primary	Blood Cytokine Level at 8 Hours Post-dose on Day 28	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	8 Hours Post-dose on Day 28	No
Primary	Blood Cytokine Level at 24 Hours Post-dose on Day 28	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	24 Hours Post-dose on Day 28	No
Primary	Blood Cytokine Level at Pre-dose on Day 35 or Early Termination	Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.	Pre-dose on Day 35 or Early Termination	No
Primary	Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1	Blood samples were collected for fluorescence-activated cell sorting [FACS] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.	Pre-dose on Day 1	No
Primary	Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	1 Hour Post-dose on Day 1	No
Primary	Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	4 Hours Post-dose on Day 1	No
Primary	Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	Pre-dose on Day 10	No
Primary	Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	Pre-dose on Day 28	No
Primary	Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	1 Hour Post-dose on Day 28	No
Primary	Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	4 Hours Post-dose on Day 28	No
Primary	Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	8 Hours Post-dose on Day 28	No
Primary	Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	24 Hours Post-dose on Day 28	No
Primary	Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination	Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.	Pre-dose on Day 35 or Early Termination	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay [ELISA] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).	Pre-dose on Day 1	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	1 Hour Post-dose on Day 1	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	4 Hours Post-dose on Day 1	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	Pre-dose on Day 10	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	Pre-dose on Day 28	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	1 Hour Post-dose on Day 28	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	4 Hours Post-dose on Day 28	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	8 Hours Post-dose on Day 28	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	24 Hours Post-dose on Day 28	No
Primary	Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination	Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.	Pre-dose on Day 35 or Early Termination	No
Primary	Parathyroid Hormone (PTH) Level at Pre-dose on Day 1	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	Pre-dose on Day 1	No
Primary	Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	1 Hour Post-dose on Day 1	No
Primary	Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	4 Hours Post-dose on Day 1	No
Primary	Parathyroid Hormone (PTH) Level at Pre-dose on Day 10	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	Pre-dose on Day 10	No
Primary	Parathyroid Hormone (PTH) Level at Pre-dose on Day 28	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	Pre-dose on Day 28	No
Primary	Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	1 Hour Post-dose on Day 28	No
Primary	Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	4 Hours Post-dose on Day 28	No
Primary	Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	8 Hours Post-dose on Day 28	No
Primary	Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	24 Hours Post-dose on Day 28	No
Primary	Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination	Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.	Pre-dose on Day 35 or Early Termination	No
Primary	Osteoprotegerin (OPG) Level at Pre-dose on Day 1	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 1	No
Primary	Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	1 Hour Post-dose on Day 1	No
Primary	Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	4 Hours Post-dose on Day 1	No
Primary	Osteoprotegerin (OPG) Level at Pre-dose on Day 10	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 10	No
Primary	Osteoprotegerin (OPG) Level at Pre-dose on Day 28	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 28	No
Primary	Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	1 Hour Post-dose on Day 28	No
Primary	Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	4 Hours Post-dose on Day 28	No
Primary	Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	8 Hours Post-dose on Day 28	No
Primary	Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	24 Hours Post-dose on Day 28	No
Primary	Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination	Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 35 or Early Termination	No
Primary	Plasma Level of Matrix Metallopeptidase (MMP13)		Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28	No
Primary	Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)		Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1	Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).	Pre-dose on Day 1	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	1 Hour Post-dose on Day 1	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	4 Hours Post-dose on Day 1	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	Pre-dose on Day 10	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	Pre-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	1 Hour Post-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	4 Hours Post-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	8 Hours Post-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	24 Hours Post-dose on Day 28	No
Primary	Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination	Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.	Pre-dose on Day 35 or Early Termination	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 1	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	1 Hour Post-dose on Day 1	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	4 Hours Post-dose on Day 1	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 10	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 28	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	1 Hour Post-dose on Day 28	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	4 Hours Post-dose on Day 28	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	8 Hours Post-dose on Day 28	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	24 Hours Post-dose on Day 28	No
Primary	Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination	Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.	Pre-dose on Day 35 or Early Termination	No
Primary	Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1	Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).	Pre-dose on Day 1	No
Primary	Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10	Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.	Pre-dose on Day 10	No
Primary	Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28	Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.	Pre-dose on Day 28	No
Primary	Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28	Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.	24 Hours Post-dose on Day 28	No
Primary	Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination	Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.	Pre-dose on Day 35 or Early Termination	No
Secondary	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).	Day 28, 35 or Early Termination	No
Secondary	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.	Day 28, 35 or Early Termination	No
Secondary	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.	Day 28, 35 or Early Termination	No
Secondary	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.	Day -7, 1 (Baseline), 28, 35 or Early Termination	No
Secondary	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.	Day 1 (Baseline), 28, 35 or Early Termination	No
Secondary	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.	Day -7, 1 (Baseline), 28, 35 or Early Termination	No
Secondary	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.	Day -7, 1 (Baseline), 28, 35 or Early Termination	No
Secondary	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.	Day 1 (Baseline), 28, 35 or Early Termination	No
Secondary	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.	Day -7, 1 (Baseline), 28, 35 or Early Termination	No

External Links

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