Phase 2
Completed N=29
A Study To Evaluate The Mechanism Of Action Of CP-690,550 In Patients With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT00976599 ↗Enrolled (actual)
29
Serious AEs
0.0%
Results posted
Jan 2013
Primary outcomePrimary: Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 — -2.73; -2.83; -3.72; -3.96 relative expression unit (REU)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Synovial Tissue Messenger Ribonucleic Acid (mRNA) Expression at Day 28 |
-2.73; -2.83; -3.72; -3.96; -2.01; -2.52 | — |
| 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 |
— | — |
| 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 |
7.33; 7.92; 31.83; 32.85; 1.50; 0.13 | — |
| PRIMARY Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Baseline (Day-7) |
0.11; 0.29; 0.41; 0.40; 0.06; 0.02 | — |
| PRIMARY Blood Levels for Gene Expression (Messenger Ribonucleic Acid [mRNA]) at Day 28 |
0.35; 0.30; 0.49; 0.40; -0.01; 0.04 | — |
| PRIMARY Blood Cytokine Level at Pre-dose on Day 1 |
0.75; 0.67; 0.42; 0.41; 0.29; 0.17 | — |
| PRIMARY Blood Cytokine Level at 1 Hour Post-dose on Day 1 |
0.76; 0.73; 0.43; 0.40; 0.29; 0.15 | — |
| PRIMARY Blood Cytokine Level at 4 Hours Post-dose on Day 1 |
0.77; 0.65; 0.43; 0.41; 0.28; 0.18 | — |
| PRIMARY Blood Cytokine Level at Pre-dose on Day 10 |
0.74; 0.69; 0.36; 0.42; 0.28; 0.19 | — |
| PRIMARY Blood Cytokine Level at Pre-dose on Day 28 |
0.69; 0.68; 0.41; 0.39; 0.24; 0.15 | — |
| PRIMARY Blood Cytokine Level at 1 Hour Post-dose on Day 28 |
0.69; 0.69; 0.40; 0.39; 0.25; 0.15 | — |
| PRIMARY Blood Cytokine Level at 4 Hours Post-dose on Day 28 |
0.67; 0.75; 0.27; 0.33; 0.22; 0.14 | — |
| PRIMARY Blood Cytokine Level at 8 Hours Post-dose on Day 28 |
0.76; 0.63; 0.29; 0.34; 0.23; 0.14 | — |
| PRIMARY Blood Cytokine Level at 24 Hours Post-dose on Day 28 |
0.73; 0.66; 0.38; 0.38; 0.26; 0.15 | — |
| PRIMARY Blood Cytokine Level at Pre-dose on Day 35 or Early Termination |
0.70; 0.66; 0.43; 0.38; 0.29; 0.14 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 1 |
214.09; 389.17; 1516.27; 1579.00; 402.73; 376.67 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 1 |
207.07; 312.69; 1533.53; 1596.54; 431.07; 372.38 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 1 |
222.79; 380.33; 1841.07; 1710.42; 505.64; 393.00 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 10 |
290.50; 310.92; 1732.29; 1477.08; 413.64; 384.15 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at Pre-dose on Day 28 |
399.62; 392.25; 1730.38; 1451.92; 363.85; 346.58 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 1 Hour Post-dose on Day 28 |
343.21; 329.00; 1705.57; 1630.64; 409.71; 482.07 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 4 Hours Post-dose on Day 28 |
336.45; 347.67; 1483.00; 1445.83; 355.27; 346.00 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 8 Hours Post-dose on Day 28 |
382.33; 318.27; 1557.58; 1616.00; 348.33; 420.18 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts at 24 Hours Post-dose on Day 28 |
276.00; 300.92; 1044.08; 1619.33; 239.92; 382.75 | — |
| PRIMARY Blood T, B and NK Lymphocyte Counts and Possible Subsets at Pre-dose on Day 35 or Early Termination |
173.86; 344.17; 1044.07; 1411.75; 253.64; 364.92 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 1 |
38.31; 24.52; 19.54; 18.54; 108.40; 98.11 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 1 |
37.30; 22.42; 18.90; 18.01; 101.10; 94.37 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 1 |
36.98; 22.09; 18.17; 19.01; 99.82; 95.23 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 10 |
32.10; 21.05; 21.35; 18.60; 91.13; 91.12 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 28 |
25.18; 19.26; 22.05; 16.51; 78.23; 79.93 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 1 Hour Post-dose on Day 28 |
21.59; 18.86; 21.45; 17.37; 78.60; 86.66 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 4 Hours Post-dose on Day 28 |
19.71; 16.67; 21.09; 15.45; 71.52; 86.56 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 8 Hours Post-dose on Day 28 |
17.94; 16.68; 20.93; 16.67; 75.32; 89.84 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at 24 Hours Post-dose on Day 28 |
24.48; 26.20; 20.96; 17.49; 82.60; 95.51 | — |
| PRIMARY Matrix Metallopeptidase 3 (MMP3), Osteocalcin and Osteopontin Levels at Pre-dose on Day 35 or Early Termination |
28.98; 28.72; 21.79; 16.60; 95.93; 86.48 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at Pre-dose on Day 1 |
38.40; 33.32 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 1 |
33.89; 31.48 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 1 |
32.97; 33.35 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at Pre-dose on Day 10 |
34.93; 31.48 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at Pre-dose on Day 28 |
38.46; 33.39 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 1 Hour Post-dose on Day 28 |
37.97; 33.93 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 4 Hours Post-dose on Day 28 |
38.70; 36.65 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 8 Hours Post-dose on Day 28 |
37.76; 37.82 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at 24 Hours Post-dose on Day 28 |
35.91; 36.08 | — |
| PRIMARY Parathyroid Hormone (PTH) Level at Pre-dose on Day 35 or Early Termination |
37.30; 34.59 | — |
| PRIMARY Osteoprotegerin (OPG) Level at Pre-dose on Day 1 |
5.99; 6.21 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 1 |
6.13; 5.72 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 1 |
5.50; 5.35 | — |
| PRIMARY Osteoprotegerin (OPG) Level at Pre-dose on Day 10 |
6.02; 5.82 | — |
| PRIMARY Osteoprotegerin (OPG) Level at Pre-dose on Day 28 |
5.53; 5.64 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 1 Hour Post-dose on Day 28 |
5.72; 5.56 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 4 Hours Post-dose on Day 28 |
5.18; 5.69 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 8 Hours Post-dose on Day 28 |
4.64; 5.64 | — |
| PRIMARY Osteoprotegerin (OPG) Level at 24 Hours Post-dose on Day 28 |
7.22; 6.20 | — |
| PRIMARY Osteoprotegerin(OPG) Level at Pre-dose on Day 35 or Early Termination |
6.31; 5.65 | — |
| PRIMARY Plasma Level of Matrix Metallopeptidase (MMP13) |
— | — |
| PRIMARY Plasma Level of Interleukin-34 (IL-34) and Interleukin-18 (IL-18) |
— | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 1 |
26383.03; 23427.00; 0.43; 0.37 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 1 |
25716.93; 23308.57; 0.36; 0.32 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 1 |
26460.26; 27297.36; 0.25; 0.25 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 10 |
5968.89; 31666.50; 0.34; 0.35 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 28 |
4094.94; 14818.88; 0.36; 0.35 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 1 Hour Post-dose on Day 28 |
3921.49; 18976.74; 0.32; 0.35 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 4 Hours Post-dose on Day 28 |
4042.21; 20123.97; 0.29; 0.20 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 8 Hours Post-dose on Day 28 |
4113.05; 15403.08; 0.28; 0.31 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at 24 Hours Post-dose on Day 28 |
6643.14; 14627.28; 0.28; 0.28 | — |
| PRIMARY Serum Amyloid A (SAA) and Carboxy-Terminal Collagen Crosslinks-1 (CTX-1) Levels at Pre-dose on Day 35 or Early Termination |
22174.19; 33853.61; 0.27; 0.34 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 1 |
545.71; 449.38; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 1 |
565.43; 479.93; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 1 |
518.29; 477.25; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 10 |
487.00; 465.00; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 28 |
437.73; 617.38; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 1 Hour Post-dose on Day 28 |
421.00; 501.31; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 4 Hours Post-dose on Day 28 |
388.15; 552.85; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 8 Hours Post-dose on Day 28 |
399.08; 414.67; 8.00; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at 24 Hours Post-dose on Day 28 |
500.38; 462.57; 8.26; 8.00 | — |
| PRIMARY Interleukin-1 Receptor Antagonist (IL-1ra) and Interleukin-15 (IL-15) Levels at Pre-dose on Day 35 or Early Termination |
520.87; 486.57; 8.00; 8.00 | — |
| PRIMARY Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 1 |
454.74; 345.87 | — |
| PRIMARY Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 10 |
318.10; 423.76 | — |
| PRIMARY Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 28 |
320.42; 409.89 | — |
| PRIMARY Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at 24 Hours Post-dose on Day 28 |
267.86; 284.87 | — |
| PRIMARY Urine Collagen Type II C-telopeptide Fragments (uCTX-II) at Pre-dose on Day 35 or Early Termination |
278.55; 340.83 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 20% Response |
60.0; 0.0; 33.3; 0.0 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response |
40.0; 0.0; 13.3; 0.0 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response |
6.7; 0.0; 6.7; 0.0 | — |
| SECONDARY Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) |
5.58; 5.06; 5.57; 5.22; 4.06; 4.91 | — |
| 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 |
-1.51; -0.31; -0.66; -0.43 | — |
| 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 |
0.0; 7.1; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) |
6.60; 6.17; 6.55; 6.32; 4.90; 6.03 | — |
| 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 |
-1.58; -0.30; -0.73; -0.32 | — |
| 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 |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
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 .
Data sourced from ClinicalTrials.gov (NCT00976599). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.