Phase 2
Completed N=45
Extension Study Of Stage 1 Subjects Of Study A3921009 For The Prevention Of Acute Rejection In Kidney Transplant Patient
Source: ClinicalTrials.gov NCT00263328 ↗Enrolled (actual)
45
Serious AEs
55.6%
Results posted
Jul 2015
Primary outcomePrimary: Calculated Glomerular Filtration Rate (GFR) Using the Modification of Diet in Renal Disease (MDRD) Equation — 67.06; 65.99; 67.05; 64.97 mL/min/1.73 m^2
Summary
A new immunosuppressive drug, based on the inhibition of an important enzyme in the immune system called JAK3, is being developed by Pfizer to prevent transplant rejection. In study A3921009, kidney transplant patients were given a JAK inhibitor or tacrolimus for 6 months posttransplant. Patients who completed study A3921009 were offered the opportunity to participate in study A3921021 which will extend the evaluation of safety and efficacy of CP-690,550 versus tacrolimus through 8 years posttransplant. In treatment group 1 (control arm), subjects will continue to receive tacrolimus. In treatment groups 2 and 3, subjects will continue to receive CP-690,550. Per Amendment 4, the tacrolimus comparator arm will be discontinued.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Calculated Glomerular Filtration Rate (GFR) Using the Modification of Diet in Renal Disease (MDRD) Equation |
67.06; 65.99; 67.05; 64.97; 65.16; 63.50 | — |
| PRIMARY Serum Creatinine Levels |
1.26; 1.19; 1.28; 1.34; 1.21; 1.33 | — |
| PRIMARY Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit |
0.00; 0.00; 0.00; 11.11; 0.00; 7.69 | — |
| PRIMARY Kaplan-Meier Analysis of Percentage of Participants With New Onset Diabetes Mellitus, Definition 1 (NODM-1) by Visit |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| PRIMARY Percentage of Participants With Hypercholesterolemia |
11.1; 35.7; 15.4; 5.6; 28.6; 8.3 | — |
| PRIMARY Percentage of Participants With Hypertriglyceridemia by Visit |
11.1; 50.0; 38.5; 5.6; 42.9; 33.3 | — |
| PRIMARY Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit |
0.00; 0.00; 0.00; 5.56; 0.00; 0.00 | — |
| PRIMARY Kaplan-Meier Analysis of Percentage of Participants With Treatment Failure by Visit |
0.00; 0.00; 0.00; 5.56; 0.00; 0.00 | — |
| SECONDARY Calculated GFR Using the Nankivell Equation (mL/Min) |
77.98; 80.15; 81.39; 73.64; 80.02; 79.31 | — |
| SECONDARY Calculated GFR Using Cockcroft-Gault Equation (mL/Min) |
92.82; 86.74; 92.35; 87.05; 87.29; 90.36 | — |
| SECONDARY Reciprocal of Serum Creatinine |
0.83; 0.88; 0.83; 0.78; 0.88; 0.80 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With NODM, Definition 2 (NODM-2) by Visit |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Total Cholesterol Levels by Visit |
187.94; 233.71; 198.58; 180.31; 228.57; 210.08 | — |
| SECONDARY Low-Density Lipoprotein (LDL) Levels by Visit |
107.11; 138.83; 109.82; 102.75; 130.21; 119.42 | — |
| SECONDARY High-Density Lipoprotein (HDL) Levels by Visit |
54.83; 59.93; 52.58; 51.81; 62.07; 56.00 | — |
| SECONDARY Ratio of Total Serum Cholesterol Level to HDL Level by Visit |
3.62; 4.09; 4.08; 3.72; 3.92; 4.03 | — |
| SECONDARY Percentage of Participants With Ratio of Total Serum Cholesterol to Serum HDL Cholesterol <5 by Visit |
94.4; 71.4; 66.7; 87.5; 85.7; 75.0 | — |
| SECONDARY Ratio of Serum LDL Level to HDL Level by Visit |
2.09; 2.42; 2.17; 2.14; 2.24; 2.31 | — |
| SECONDARY Percentage of Participants With Ratio of Serum LDL Cholesterol to Serum HDL Cholesterol <3.5 by Visit |
94.4; 75.0; 90.9; 93.8; 85.7; 83.3 | — |
| SECONDARY Serum Triglyceride Levels by Visit |
129.44; 205.07; 194.00; 129.19; 181.86; 173.00 | — |
| SECONDARY Percentage of Participants Requiring Lipid-Lowering Agents by Visit |
38.9; 64.3; 53.8; 44.4; 64.3; 53.8 | — |
| SECONDARY Percentage of Participants Requiring Anti-Hypertensive Medication by Visit |
83.3; 85.7; 92.3; 83.3; 85.7; 92.3 | — |
| SECONDARY Percentage of Participants Requiring Diabetes Agents (Oral Hypoglycemic Agents, Anti-Diabetic Agents, or Insulin) by Visit |
5.6; 35.7; 30.8; 5.6; 35.7; 33.3 | — |
| SECONDARY Epstein Barr Virus (EBV) Deooxyribonucleic Acid (DNA) Levels Determined Using Polymerase Chain Reaction (PCR) by Visit |
0.41; 1.00; 3.17; 0.12; 4.07; 8.42 | — |
| SECONDARY Percentage of Participants With EBV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit |
88.2; 71.4; 33.3; 94.1; 64.3; 33.3 | — |
| SECONDARY BK Virus (BKV) DNA Levels Determined Using PCR by Visit |
1.29; 1.58; 2.23; 0.10; 2.85; 0.75 | — |
| SECONDARY Percentage of Participants With BKV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit |
100.0; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With Cytomegalovirus (CMV) Disease by Visit |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With First Biopsy-Proven Chronic Allograft Nephropathy (BPCAN) by Visit |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Cumulative Percentage of Participants With a First Antibody-Mediated Rejection or First BPAR |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cumulative Percentage of Participants With Ordered Categorical Severity of First BPCAN |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit |
0.00; 0.00; 0.00; 5.56; 0.00; 0.00 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With Graft Survival by Visit |
100.00; 100.00; 100.00; 100.00; 100.00; 100.00 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit |
100.00; 100.00; 100.00; 100.00; 100.00; 100.00 | — |
| SECONDARY Kaplan-Meier Analysis of Percentage of Participants With Rejection by Visit |
0.00; 0.00; 0.00; 5.56; 7.14; 0.00 | — |
| SECONDARY Absolute Cluster of Differentiation (CD) 8+, CD19+, CD4+, and CD56+ Flouresence Activated Cell Sorting (FACS) Counts (Cells/uL) by Visit |
284.67; 207.43; 232.33; 318.20; 224.36; 238.08 | — |
| SECONDARY Hemoglobin A1c (HbA1c) Levels by Visit |
5.65; 6.84; 6.02; 5.63; 7.12; 6.28 | — |
| SECONDARY Homeostatic Model Assessment (HOMA)-%B by Visit |
204.67; 142.23; 194.65; 224.75; 138.10; 165.38 | — |
| SECONDARY Ratio of Fasting Serum Proinsulin (Pmol/L) to Insulin (Pmol/L) by Visit |
0.15; 0.32; 0.40; 0.64; 0.30; 0.22 | — |
| SECONDARY Area Under the Curve (AUC) of Serum Glucose (mg*h/dL) Measured During Oral Glucose Tolerance Test (OGTT) by Visit |
234.78; 254.25; 281.54; 230.10; 236.94; 281.90 | — |
| SECONDARY AUC of Serum Insulin (microU*h/mL) Measured During OGTT by Visit |
85.05; 99.96; 153.46; 79.84; 130.63; 181.70 | — |
| SECONDARY HOMA Insulin Resistance (IR) by Visit |
2.55; 2.24; 2.54; 2.67; 9.01; 2.68 | — |
| SECONDARY Fasting Serum Glucose Levels (mg/dL) by Visit |
96.89; 115.14; 97.90; 103.00; 133.79; 102.75 | — |
| SECONDARY Tofacitinib Concentrations in Plasma (ng/mL) by Visit |
40.97; 12.38; NA; 24.00; 14.75; 32.86 | — |
| SECONDARY Trough Levels of Tacrolimus (ng/mL) by Visit |
7.00; 9.50; 8.00; 8.78; 6.17; 6.87 | — |
| SECONDARY Short-Form 36 Version 2 (SF-36 v2) Mental Component Summary (MCS) and Physical Component Summary (PCS) Scores by Visit and Scale |
54.33; 51.71; 46.05; 53.76; 50.67; 46.89 | — |
| SECONDARY Change From Baseline in SF-36 v2 MCS and PCS Scores by Visit and Scale |
9.61; 6.23; 3.20; 10.82; 5.65; 2.76 | — |
| SECONDARY SF-36 v2 Subscale Scores by Visit |
53.49; 47.82; 47.56; 53.16; 50.29; 44.42 | — |
| SECONDARY Change From Baseline in SF-36 v2 Subscale Scores by Visit |
8.82; 0.51; 5.23; 9.90; 4.50; 2.56 | — |
| SECONDARY End Stage Renal Disease Symptom Checklist (ESRD-SCL) Transplanation Module Scores by Visit and Scale |
0.22; 0.37; 0.29; 0.53; 0.41; 0.46 | — |
| SECONDARY Change From Baseline in ESRD-SCL Transplantation Module Scores by Visit and Scale |
-0.34; -0.34; -0.53; -0.20; -0.36; -0.30 | — |
| SECONDARY Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using Health Care Resource Utilization (HCRU) Questionnaire |
3.1; 2.7; 6.3; 7.2; 6.4; 5.8 | — |
Eligibility Criteria
Inclusion Criteria
- Enrollment in Stage 1 of Study A3921009 and have completed 6-months of treatment with trial medications (CP-690,550 or tacrolimus)
- Recipient of a first-time kidney transplant
Exclusion Criteria
- Subject with any untreated condition that may affect drug absorption (eg, gastrectomy or clinically significant diabetic gastroenteropathy).
- Subjects who are on the waiting list for a second kidney transplant or any non-renal organ transplants.
Data sourced from ClinicalTrials.gov (NCT00263328). 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.