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CP-690,550

Phase 3

Rheumatoid Arthritis | Small molecule | Immunology |Pfizer, Inc.|Last Updated: May 12, 2015

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
Premium
Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
Premium
Trial Design
RandomizedDouble-BlindNO_TREATMENT_CONTROLLEDDMCBiomarker
Total Trials8
Total Enrollment1,912
FDA Designations
No designations recorded
Clinical Trials (8)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00853385A Phase 3 Study Comparing 2 Doses Of CP-690,550 And The Active Comparator, Humira (Adalimumab) Vs. Placebo For Treatment Of Rheumatoid ArthritisPHASE3 COMPLETED 717 — — May 1, 2009Mar 1, 2011Jan 18, 2013125 United States, Australia +19
NCT00661661Long-Term, Open-Label Study Of CP-690,550 For Treatment Of Rheumatoid Arthritis In JapanPHASE3 COMPLETED 487 — — Apr 1, 2008Dec 1, 2013May 12, 201556 Japan
NCT01359150A Study To Assess the Immune Response Following Administration Of Influenza and Pneumococcal Vaccines To Subjects With Rheumatoid Arthritis Receiving CP-690,550 Or PlaceboPHASE2 COMPLETED 223 — — Sep 1, 2011Feb 1, 2012Mar 29, 201357 United States, Poland
NCT01059864Study Of The Effects Of Atorvastatin On Cholesterol Levels In Rheumatoid Arthritis Patients Taking CP-690,550PHASE2 COMPLETED 111 — — Feb 1, 2010Nov 1, 2010Dec 13, 201215 United States, South Korea
NCT00976599A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid ArthritisPHASE2 COMPLETED 29 — — Nov 1, 2009Jul 1, 2011Jan 9, 201315 United States
NCT00147498Three Dose Levels of CP-690,550 Monotherapy Versus Placebo, Administered Orally Twice Daily (BID) for 6 WeeksPHASE2 COMPLETED 264 — — Jan 1, 2005Jun 1, 2006Jan 30, 201360 United States, Belgium +7
NCT01262118Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid ArthritisPHASE1 COMPLETED 69 — — May 1, 2011Feb 1, 2012Jan 23, 201311 United States, Hungary
NCT01745055Co-Administration Of Methotrexate And CP-690,550PHASE1 COMPLETED 12 — — Apr 1, 2005Jun 1, 2006Feb 4, 20134 United States
Unlock Drug Trial Details
Study Endpoints
Primary Endpoints
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6
Month 6

ACR20 response: greater than or equal to (\>=) 20% 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). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 3
Baseline, Month 3

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

Percentage of Participants With Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 6
Month 6

DAS28-4 (ESR) calculated from SJC and TJC using 28-joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and \> 3.2 to 5.1 implied moderate to high disease activity, and \< 2.6 = remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Baseline up to Week 288

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to the last participants visit in the study. The baseline data of Study A3921039, A3921040 or A3921044 were used as baseline data for safety evaluation.

Percentage of Participants With Satisfactory Humoral Response to the Pneumococcal Vaccine at Visit 3 (Day 64)
Day 64 (End of Study [EOS])

Satisfactory humoral response to the pneumococcal vaccine was defined as greater than or equal to (\>=) 2 fold increase in antibody concentrations from vaccination baseline (Day 29) in at least 6 of 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C). Data was stratified by the background methotrexate use.

Percentage of Participants With Satisfactory Humoral Response to the Seasonal Influenza Vaccine at Visit 3 (Day 64)
Day 64 (EOS)

Satisfactory humoral response to the influenza vaccine was defined as \>= 4 fold increase in antibody titers from vaccination baseline (Day 29) in at least 2 of 3 influenza antigens (B, H1N1, H3N2). Data was stratified by the background methotrexate use.

Percent Change From Baseline (Week 6) in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Week 12
Baseline (Week 6), Week 12
Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28
Day -7 (Baseline), Day 28

Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.

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
Baseline (Day -7), Day 28

Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.

Change From Baseline in Percentage of Area Stained For CD3+ and CD68+ Surface Markers of Inflammatory Cells of the Synovial Tissue at Day 28
Baseline (Day -7), Day 28

The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.

Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18)
Pre-dose on Day 1, 10, 28 and 35 or Early Termination; 1, 4 hours Post-dose on Day 1, 28; 8, 24 hours Post-dose on Day 28
Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 6
Week 6

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joints count (TJC); \>= 20% improvement in swollen joints 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).

High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline
Baseline

Blood level of HDL-C was measured following a 12-hours fasting.

High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6
Week 6

Blood level of HDL-C was measured following a 12-hours fasting.

Cholesterol Ester Production Rate at Baseline
Baseline

Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.

Cholesterol Ester Production Rate at Week 6
Week 6

Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.

Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] for CP-690,550
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7

AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).

Maximum Observed Plasma Concentration (Cmax) for CP-690,550
0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 8 and 12 hours post-dose on Day 6 and Day 7
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Methotrexate (MTX)
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours post-dose on Day 1 and Day 7

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

Maximum Observed Plasma Concentration (Cmax) for Methotrexate (MTX)
0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 24 and 48 hours post-dose on Day 1 and Day 7
Secondary Endpoints
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 1 and 3
Month 1, 3
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 9 and 12
Month 9, 12
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 1, 3 and 6
Month 1, 3, 6
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
5mgEXPERIMENTAL -
10 mgEXPERIMENTAL -
Placebo Sequence 1PLACEBO_COMPARATOR -
Placebo Sequence 2PLACEBO_COMPARATOR -
adalimumabACTIVE_COMPARATOR -
CP-690,550EXPERIMENTAL -
Treatment Group 1: 10 mg BID CP-690,550 (100 subjects).EXPERIMENTALCP-690,550 will be administered for 4 weeks, vaccines will be administered at week 4. CP-690,550 will then continue for another 5 weeks at which point the immune response will be evaluated.
Treatment Group 2:Placebo CP-690,550 (100 subjects).PLACEBO_COMPARATORPlacebo will be administered for 4 weeks, vaccines will be administered at week 4. Placebo will then continue for another 5 weeks at which point the immune response will be evaluated.
Arm 1EXPERIMENTAL -
Arm 2EXPERIMENTAL -
CP-690,550 + methotrexateEXPERIMENTAL -
Placebo + methotrexatePLACEBO_COMPARATOR -
5 mg BIDEXPERIMENTALCP 690,550 5 mg BID
15 mg BIDEXPERIMENTALCP 690,550 15 mg BID
30 mg BIDEXPERIMENTALOral tablets administered at a dose of 30 mg BID for 6 weeks
PlaceboPLACEBO_COMPARATORPlacebo
CP-690,550 (tasocitinib) 10 mg twice daily (BID)EXPERIMENTAL -
Healthy VolunteersNO_INTERVENTIONNo intervention
CP-690,550 (tofacitinib) 30 mg q12hEXPERIMENTALIndividual dose of methotrexate with the addition of CP-690,550 30 mg q12h
Interventions
NameTypeDescription
CP 690,550DRUGtablets 5 mg BID PO plus q2 week placebo SC injections for 12 months
CP-690,550DRUGtablets 10 mg BID PO plus q2 week placebo SC injections for 12 months
PlaceboOTHERplacebo tablets BID PO advance to 5mg CP 690,550 BID at Month 3 or 6 visit plus q2 week placebo SC injections for 12 months
Biologic TNFiBIOLOGICALplacebo tablets BID PO plus adalimumab 40 mg q2 week SC injections for 12 months
AtorvastatinDRUGStarting at Week 6 and continuing through Week 12 atorvastatin 10 mg oral tablets administered once daily
Atorvastatin PlaceboDRUGStarting at Week 6 and continuing through Week 12 atorvastatin placebo tablets administered once daily
CP-690,550 + methotrexateDRUGCP-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 + MethotrexateDRUGMethotrexate dose is ≥ 7.5 mg / week and ≤ 25 mg / week
CP-690,550 (tasocitinib)DRUGCP-690,550 (tasocitinib) dosed at 10 mg BID for 6 weeks in patients with active rheumatoid arthritis
CP-690,550 (tofacitinib)DRUGCP-690,550 30 mg q12h for 5 days
Methotrexate (MTX)DRUGindividual dose of methotrexate (stably dosed)
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites125

Inclusion Criteria: * The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria. * The patient must have had an inadequate response to methotrexate and have active disease, as defined by both: ≥6 joints tender or painful on motion; and ≥6 joints s...

Countries:United StatesAustraliaBosnia and HerzegovinaBulgariaCanadaChileCosta RicaCroatiaCzechiaDenmarkDominican RepublicFinlandGermanyMexicoPhilippinesPolandSlovakiaSouth KoreaSpainThailandUnited KingdomJapanBelgiumBrazilItalyHungary
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Competitive Landscape -Rheumatoid Arthritis 97 trials
CompanyTickerTrialsLead PhaseDrugs
AbbVie, Inc.ABBV6PHASE3Upadacitinib, Adalimumab, Tocilizumab, Lutikizumab, Ravagalimab
Eli Lilly and CompanyLLY5PHASE3Baricitinib, Tocilizumab, LY3541860, LY4213663, LY4298445
Bristol-Myers Squibb CompanyBMY6PHASE3Abatacept, Adalimumab, Methotrexate, BMS-986528, CC-97540
Johnson & JohnsonJNJ2PHASE3Ustekinumab, Guselkumab
AstraZeneca PLCAZN4PHASE2AZD1163, AZD0120, AZD5492, Surovatamig
Novartis AG Sponsored ADRNVS4PHASE2VAY736 PFS, VAY736 AI, PIT565, Secukinumab
Merck & Co., Inc.MRK2PHASE2Tulisokibart, Methotrexate, MK-1045
Sanofi SA Sponsored ADRSNY3PHASE2Sarilumab SAR153191, SAR448501, Leflunomide
AnaptysBio, Inc.ANAB1PHASE2Rosnilimab
Spyre Therapeutics, IncSYRE1PHASE2SPY002-072
Immunovant IncIMVT1PHASE2IMVT-1402
XBiotech, Inc.XBIT1PHASE2Natrunix, Methotrexate
Amgen Inc.AMGN1PHASE2Inebilizumab, Blinatumomab
Artiva Biotherapeutics, Inc.ARTV2PHASE2Allogeneic NK Cells, AB-101, Rituximab, Cyclophosphamide, Fludarabine
Gilead Sciences, Inc.GILD1PHASE1GS-0151
Zenas BioPharma, Inc.ZBIO1PHASE1ZB002
Stryker CorporationSYK5NAUndisclosed
Sonoma Pharmaceuticals, Inc.SNOA2PHASE1SBT777101
Zimmer Biomet Holdings, Inc.ZBH29NAUndisclosed
Adicet Bio IncACET1PHASE1ADI-001, Fludarabine, Cyclophosphamide
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