Clinical trial NCT00263328: Extension Study Of Stage 1 Subjects Of Study A3921009 For The Prevention Of Acute Rejection In Kidney Transplant Patient
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplantation
Keywords: immunosuppression
JAK3 inhibitor
kidney transplant
tofacitinib
Xeljanz
CP-690
550
tacromilus
mycophenolate mofetil
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-12-08
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


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.

Primary outcomes:
measure: Calculated Glomerular Filtration Rate (GFR) Using the Modification of Diet in Renal Disease (MDRD) Equation
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Serum Creatinine Levels
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants With New Onset Diabetes Mellitus, Definition 1 (NODM-1) by Visit
timeFrame: 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
measure: Percentage of Participants With Hypercholesterolemia
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96, and Follow-Up (Month 98)
measure: Percentage of Participants With Hypertriglyceridemia by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants With Treatment Failure by Visit
timeFrame: 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
Secondary outcomes:
measure: Calculated GFR Using the Nankivell Equation (mL/Min)
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Calculated GFR Using Cockcroft-Gault Equation (mL/Min)
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Reciprocal of Serum Creatinine
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Kaplan-Meier Analysis of Percentage of Participants With NODM, Definition 2 (NODM-2) by Visit
timeFrame: 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
measure: Total Cholesterol Levels by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Low-Density Lipoprotein (LDL) Levels by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: High-Density Lipoprotein (HDL) Levels by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Ratio of Total Serum Cholesterol Level to HDL Level by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Percentage of Participants With Ratio of Total Serum Cholesterol to Serum HDL Cholesterol <5 by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Ratio of Serum LDL Level to HDL Level by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Percentage of Participants With Ratio of Serum LDL Cholesterol to Serum HDL Cholesterol <3.5 by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Serum Triglyceride Levels by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Percentage of Participants Requiring Lipid-Lowering Agents by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
measure: Percentage of Participants Requiring Anti-Hypertensive Medication by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
measure: Percentage of Participants Requiring Diabetes Agents (Oral Hypoglycemic Agents, Anti-Diabetic Agents, or Insulin) by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
measure: Epstein Barr Virus (EBV) Deooxyribonucleic Acid (DNA) Levels Determined Using Polymerase Chain Reaction (PCR) by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96
measure: Percentage of Participants With EBV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96 and Follow-Up (Month 98)
measure: BK Virus (BKV) DNA Levels Determined Using PCR by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Percentage of Participants With BKV DNA Determined Using PCR by Specific Cutoff Categories (in Number of Copies/PCR) and Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Kaplan-Meier Analysis of Percentage of Participants With Cytomegalovirus (CMV) Disease by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants With First Biopsy-Proven Chronic Allograft Nephropathy (BPCAN) by Visit
timeFrame: 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
measure: Cumulative Percentage of Participants With a First Antibody-Mediated Rejection or First BPAR
timeFrame: Months 12, 18, 24, 36, 48, 60, 72, 84, 96, and Follow-Up (Month 98)
measure: Cumulative Percentage of Participants With Ordered Categorical Severity of First BPCAN
timeFrame: Months 12, 18, 24, 36, 48, 60, 72, 84, and 96
measure: Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants With Graft Survival by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit
timeFrame: 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
measure: Kaplan-Meier Analysis of Percentage of Participants With Rejection by Visit
timeFrame: 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
measure: Absolute Cluster of Differentiation (CD) 8+, CD19+, CD4+, and CD56+ Flouresence Activated Cell Sorting (FACS) Counts (Cells/uL) by Visit
timeFrame: Months 12 and 24
measure: Hemoglobin A1c (HbA1c) Levels by Visit
timeFrame: Months 12, 24, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96 and Follow-up (Month 98)
measure: Homeostatic Model Assessment (HOMA)-%B by Visit
timeFrame: Months 12 and 24
measure: Ratio of Fasting Serum Proinsulin (Pmol/L) to Insulin (Pmol/L) by Visit
timeFrame: Months 12 and 24
measure: Area Under the Curve (AUC) of Serum Glucose (mg*h/dL) Measured During Oral Glucose Tolerance Test (OGTT) by Visit
timeFrame: Months 12 and 24
measure: AUC of Serum Insulin (microU*h/mL) Measured During OGTT by Visit
timeFrame: Months 12 and 24
measure: HOMA Insulin Resistance (IR) by Visit
timeFrame: Months 12 and 24
measure: Fasting Serum Glucose Levels (mg/dL) by Visit
timeFrame: Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)
measure: Tofacitinib Concentrations in Plasma (ng/mL) by Visit
timeFrame: Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-up (Month 98)
measure: Trough Levels of Tacrolimus (ng/mL) by Visit
timeFrame: Months 9, 12, 18, 24, 30, 36, 42, 48, 54, 60, and 72 and Follow-up (Month 98)
measure: Short-Form 36 Version 2 (SF-36 v2) Mental Component Summary (MCS) and Physical Component Summary (PCS) Scores by Visit and Scale
timeFrame: Months 12, 18, and 24
measure: Change From Baseline in SF-36 v2 MCS and PCS Scores by Visit and Scale
timeFrame: Baseline, Months 12, 18, and 24
measure: SF-36 v2 Subscale Scores by Visit
timeFrame: Months 12, 18, and 24
measure: Change From Baseline in SF-36 v2 Subscale Scores by Visit
timeFrame: Baseline, Months 12, 18, and 24
measure: End Stage Renal Disease Symptom Checklist (ESRD-SCL) Transplanation Module Scores by Visit and Scale
timeFrame: Months 12, 18, and 24
measure: Change From Baseline in ESRD-SCL Transplantation Module Scores by Visit and Scale
timeFrame: Baseline, Months 12, 18, and 24
measure: Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using Health Care Resource Utilization (HCRU) Questionnaire
timeFrame: Months 12, 18, and 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Multi Organ Transplant Center
state: California
city: Los Angeles
country: United States
facility: St. Vincent Medical Center
state: California
city: Los Angeles
country: United States
facility: Transplant Research Institute
state: California
city: Palo Alto
country: United States
facility: Stanford School of Medicine
state: California
city: San Diego
country: United States
facility: Balboa Institute of Transplantation
state: California
city: San Diego
country: United States
facility: California Institute of Renal Research
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, Kidney Transplant Unit
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center Renal Clinical Trials Office
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University-Feinberg School of Medicine, Division of Organ Transplantation
state: Illinois
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Jack J Dreyfus Clinic
state: New York
city: New York
country: United States
facility: Recanati/Miller Transplantation Institute
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital / Weill Cornell Medical Center
state: New York
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Transplant Services
state: Oregon
city: Portland
country: United States
facility: Northwest Renal Clinic
state: Oregon
city: Dallas
country: United States
facility: Dallas Transplant Institute
state: Texas
city: Dallas
country: United States
facility: Annette C & Harold C Simmons Transplant Institute
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Busque S, Leventhal J, Brennan DC, Steinberg S, Klintmalm G, Shah T, Mulgaonkar S, Bromberg JS, Vincenti F, Hariharan S, Slakey D, Peddi VR, Fisher RA, Lawendy N, Wang C, Chan G. Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in de novo kidney allograft recipients. Am J Transplant. 2009 Aug;9(8):1936-45. doi: 10.1111/j.1600-6143.2009.02720.x.