A Multicenter, Phase 2, Open-label, Controlled, Extension Study For Stage 1 Subjects Of Study A3921009 To Evaluate The Long-term Safety And Efficacy Of Cp-690,550 Versus Tacrolimus, When Co-administered With Mycophenolate Mofetil In Renal Allograft Recipients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 46
- 试验地点
- 27
- 主要终点
- Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Treatment group 1
Standard of care
干预措施: Tacrolimus (Drug)
Treatment group 2
Treatment group 2 also receives mycophenolate mofetil
干预措施: CP-690,550 (Drug)
Treatment group 3
Treatment group 3 does not receive mycophenolate mofetil
干预措施: CP-690,550 (Drug)
结局指标
主要结局
Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit
时间窗: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
Kaplan-Meier analysis of percentage of participants with clinically significant infections by time to first clinically significant infection within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.
Calculated Glomerular Filtration Rate (GFR) Using the Modification of Diet in Renal Disease (MDRD) Equation
时间窗: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR by MDRD equation = 170 \* (serum creatinine \[in milligrams per deciliter (mg/dL)\])\^(-0.999) \* (age in years)\^(-0.176) \* (0.762 if female) \* (1.18 if black) \* (blood urea nitrogen \[BUN\] concentration \[mg/dL\])\^(-0.170) \* (serum albumin concentration \[in grams per dL (g/dL)\])\^(0.318). A normal GFR is \>90 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR \<15 mL/min/1.73 m\^2 indicated kidney failure.
Serum Creatinine Levels
时间窗: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
Kaplan-Meier Analysis of Percentage of Participants With New Onset Diabetes Mellitus, Definition 1 (NODM-1) by Visit
时间窗: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
Kaplan-Meier analysis of time to NODM-1 within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. NODM-1 was defined as an event experienced by participants who were non-diabetic prior to transplantation and required treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin for greater than or equal to (≥)30 days.
Percentage of Participants With Hypertriglyceridemia by Visit
时间窗: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
Hypertriglyceridemia was defined as triglyceride levels of \>200 mg/dL or 2.3 mmol/L.
Kaplan-Meier Analysis of Percentage of Participants With Treatment Failure by Visit
时间窗: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
Kaplan-Meier analysis of percentage of participants with treatment failure by time to treatment failure within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Treatment failure was defined as the first occurrence of BPAR, death, graft loss or premature discontinuation of trial medication for any reason.
Percentage of Participants With Hypercholesterolemia
时间窗: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96, and Follow-Up (Month 98)
Hypercholesterolemia was defined as cholesterol levels \>240 mg/dL or 6.2 mmol/L.
Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit
时间窗: Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
Kaplan-Meier analysis of percentage of participants with first BPAR by time to first BPAR within 96 months post-transplant. BPAR was defined as acute/active cellular rejection (Category 4 of the Banff Classification), based on the assessment of the renal allograft biopsy by a central, blinded pathologist. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.
次要结局
- Calculated GFR Using the Nankivell Equation (mL/Min)(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Reciprocal of Serum Creatinine(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Serum Triglyceride Levels by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Percentage of Participants With EBV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96 and Follow-Up (Month 98))
- Percentage of Participants With Ratio of Serum LDL Cholesterol to Serum HDL Cholesterol <3.5 by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Calculated GFR Using Cockcroft-Gault Equation (mL/Min)(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Kaplan-Meier Analysis of Percentage of Participants With NODM, Definition 2 (NODM-2) by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Low-Density Lipoprotein (LDL) Levels by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Ratio of Total Serum Cholesterol Level to HDL Level by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Percentage of Participants Requiring Anti-Hypertensive Medication by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Total Cholesterol Levels by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- High-Density Lipoprotein (HDL) Levels by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Percentage of Participants With Ratio of Total Serum Cholesterol to Serum HDL Cholesterol <5 by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Ratio of Serum LDL Level to HDL Level by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Absolute Cluster of Differentiation (CD) 8+, CD19+, CD4+, and CD56+ Flouresence Activated Cell Sorting (FACS) Counts (Cells/uL) by Visit(Months 12 and 24)
- Homeostatic Model Assessment (HOMA)-%B by Visit(Months 12 and 24)
- Ratio of Fasting Serum Proinsulin (Pmol/L) to Insulin (Pmol/L) by Visit(Months 12 and 24)
- Change From Baseline in SF-36 v2 MCS and PCS Scores by Visit and Scale(Baseline, Months 12, 18, and 24)
- Percentage of Participants Requiring Diabetes Agents (Oral Hypoglycemic Agents, Anti-Diabetic Agents, or Insulin) by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Percentage of Participants With BKV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Cumulative Percentage of Participants With a First Antibody-Mediated Rejection or First BPAR(Months 12, 18, 24, 36, 48, 60, 72, 84, 96, and Follow-Up (Month 98))
- Fasting Serum Glucose Levels (mg/dL) by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Short-Form 36 Version 2 (SF-36 v2) Mental Component Summary (MCS) and Physical Component Summary (PCS) Scores by Visit and Scale(Months 12, 18, and 24)
- Percentage of Participants Requiring Lipid-Lowering Agents by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- BK Virus (BKV) DNA Levels Determined Using PCR by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98))
- Area Under the Curve (AUC) of Serum Glucose (mg*h/dL) Measured During Oral Glucose Tolerance Test (OGTT) by Visit(Months 12 and 24)
- AUC of Serum Insulin (microU*h/mL) Measured During OGTT by Visit(Months 12 and 24)
- Trough Levels of Tacrolimus (ng/mL) by Visit(Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 72 and Follow-up (Month 98))
- Epstein Barr Virus (EBV) Deooxyribonucleic Acid (DNA) Levels Determined Using Polymerase Chain Reaction (PCR) by Visit(Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Kaplan-Meier Analysis of Percentage of Participants With First Biopsy-Proven Chronic Allograft Nephropathy (BPCAN) by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Kaplan-Meier Analysis of Percentage of Participants With Graft Survival by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Hemoglobin A1c (HbA1c) Levels by Visit(Months 12, 24, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 and Follow-up (Month 98))
- Tofacitinib Concentrations in Plasma (ng/mL) by Visit(Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-up (Month 98))
- Change From Baseline in ESRD-SCL Transplantation Module Scores by Visit and Scale(Baseline, Months 12, 18, and 24)
- Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using Health Care Resource Utilization (HCRU) Questionnaire(Months 12, 18, and 24)
- Kaplan-Meier Analysis of Percentage of Participants With Cytomegalovirus (CMV) Disease by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- Cumulative Percentage of Participants With Ordered Categorical Severity of First BPCAN(Months 12, 18, 24, 36, 48, 60, 72, 84, and 96)
- Kaplan-Meier Analysis of Percentage of Participants With Rejection by Visit(Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96)
- HOMA Insulin Resistance (IR) by Visit(Months 12 and 24)
- SF-36 v2 Subscale Scores by Visit(Months 12, 18, and 24)
- Change From Baseline in SF-36 v2 Subscale Scores by Visit(Baseline, Months 12, 18, and 24)
- End Stage Renal Disease Symptom Checklist (ESRD-SCL) Transplanation Module Scores by Visit and Scale(Months 12, 18, and 24)