Extension Study Of Subjects From Study A3921030 For The Prevention Of Acute Rejection In Kidney Transplant Patients
- Registration Number
- NCT00658359
- Lead Sponsor
- Pfizer
- Brief Summary
This is a study that will follow transplant patients from Study A3921030 to monitor for long term safety, tolerability and efficacy for 5 additional years, except in Portugal where the study will follow transplant patients through Month 36 posttransplant. Patients will continue their study medications that were previously assigned.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 178
- Subjects who successfully completed Study A3921030
- Subjects who are on the waiting list for a second kidney transplant or any non-renal organ transplants
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm 2 CP-690,550 Treatment Arm 2 will also receive standard of care medications Treatment Arm 3 CP-690,550 Treatment Arm 3 will also receive standard of care medications Treatment Arm 1 Cyclosporine Treatment Arm 1 will also receive standard of care medications
- Primary Outcome Measures
Name Time Method Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infection by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Clinically significant infection was defined as the presence of documented infection confirmed by culture, biopsy, genomic, or serologic findings post-randomization and requiring hospitalization or parenteral anti-infective treatment, or otherwise deemed significant by the investigator. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.
Percentage of Participants With Malignancies Months 12 through 72. All treatment-emergent malignancies in Study A3921050 were included as collected on the Malignancy Case Report Form page.
Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters Per Minute [mL/Min]) Month 36 Glomerular filtration rate (GFR): an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous (IV) bolus over 5 minutes immediately after morning dosing of Tofacitinib or CsA on day of GFR evaluation. Blood samples for iohexol (3 millilitres \[mL\] each to provide a minimum of 1 mL serum) were collected into appropriately labeled tubes containing no additives at 120, 180, 240, and 300 minutes after the end of the iohexol IV bolus. A normal GFR is greater than (\>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (\<) 15 mL/min indicated kidney failure.
Percentage of Participants With Progression of Chronic Allograft Lesions at Month 36 Month 36 Progression of chronic allograft lesions was defined as an increase in the Banff chronicity score (Banff-CS) in biopsy from the implantation (baseline) biopsy in a given participant. Banff-CS was the sum of the Banff scores for the 4 chronic basic lesions (allograft glomerulopathy \[cg\] + interstitial fibrosis \[ci\] + tubular atrophy \[ct\] + vascular intimal thickening \[cv\]). The Banff-CS ranged from 0-12, higher score indicated greater lesions and Month 36 Banff-CS greater than the implantation biopsy score indicated progression of lesions.
Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 BPAR was category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.
Kaplan-Meier Analysis of Percentage of Participants With Treated Clinical Acute Rejection by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Treated clinical acute rejection was defined as an acute rejection episode that was diagnosed based on local biopsy readout and received anti-rejection treatment. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.
- Secondary Outcome Measures
Name Time Method Least Squares Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.
Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Efficacy failure was the first occurrence of BPAR diagnosed by the central pathologist or graft loss including participant death. BPAR (category acute rejection) was interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.
Least Squares Means of Total Serum Triglycerides (mg/dL) by Visit Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.
Mean Absolute Neutrophil Counts (ANC) (Kelvin Per Millimeter Cubed [K/mm^3]) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.
Mean Hemoglobin (Hgb) (Grams Per Deciliter [g/dL]) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.
Mean Trough Levels of Cyclosporine by Visit Predose: Months 18, 24, 36, 48, 60, 72 All CsA samples were taken predose (collected 0 to 10 minutes prior to the morning dose).
Mean Glycosylated Hemoglobin (HBA1c) (Percent [%]) by Visit Months 24, 36, 48, 60, 72 HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.
Least Squares Means of Fasting Serum Glucose Levels (mg/dL) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A compund symmetry variance-covariance structure was used.
Percentage of Participants Discontinuing From the Study Months 12 through 72. Discontinuations were due to any reason including those occurring as a result of protocol Amendments 3 and 4.
Least Squares Means of Total Serum Cholesterol Levels (Milligrams Per Deciliter [mg/dL]) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.
Least Squares Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.
Percentage of Participants by Proteinuria Category by Visit Months 24, 36, 48, 60, 72 and Follow-up Proteinuria was defined as the presence of an excess of serum proteins in the urine. Normal value of proteinuria is below 0.15 grams per 24 hours (g/24 hr). Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.
Least Square Means of Estimated GFR Calculated Using the Nankivell Equation by Visit Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Nankivell formula, where:
Creatinine clearance (mL/min) = 6.7/serum creatinine (millimols per litre \[mmol/L\]) - serum urea (mmol/dL)/2 + actual body weight (kilograms \[kg\])/4 - 100/Height (metres \[m\])\^2 + (35 for male or 25 for female).
A normal GFR for adults is \> 90 mL/min. Lower values indicate poor kidney function. A GFR \<15 is consistent with kidney failure.
Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.Kaplan-Meier Analysis of Percentage of Participants With Combined Banff Rejection by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Banff 97: standard classification for scoring and classifying rejection of kidney transplant biopsies in 6 diagnostic categories: normal, antibody-mediated rejection, borderline changes: 'suspicious' for acute cellular rejection, acute/active cellular rejection, chronic/sclerosing allograft nephropathy, and other. Combined Banff rejection was calculated from categories of antibody-mediated rejection (Category 2) plus borderline changes (Category 3) plus acute rejection (Category 4), as interpreted by the central pathologist. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.
Kaplan-Meier Analysis of Percent of Participants With Graft Survival With Death Censored by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 Graft loss was defined as graft nephrectomy, subject death, retransplantation, or return to dialysis for at least 6 consecutive weeks. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits. Included data up to 2 months postdose in the clinical Follow-up visit.
Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits. Included data up to 2 months postdose in the clinical Follow-up visit.
Least Squares Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR (mL/min) was calculated using Cockcroft-Gault equation. GFR by Cockcroft-Gault equation= body weight (kg)\*(140 minus age in years) divided by (72\*serum creatinine \[mg/dL\]). For females value obtained was multiplied by 0.85. A normal GFR is \>90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR \<15 mL/min indicated kidney failure.
Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.Least Squares Means of Estimated GFR (eGFR) (mL/Min/1.73 Square Meter [m^2]) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) Plus Imputation (eGFR=0 for Graft Loss/Death) by Visit Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR (mL/min/1.73 m\^2) by MDRD equation = 170 \* (serum creatinine \[mg/dL\])\^(-0.999) \* (age in years)\^(-0.176) \* (0.762 if female) \* (1.18 if black) \* (blood urea nitrogen concentration \[mg/dL\])\^(-0.170) \* (serum albumin concentration \[g/dL\])\^(0.318). A normal GFR is \>90 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.
Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.Least Squares Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36 Months 24, 36 SF-36 v2 is a self-administered 36-item generic health status measure with 8 general health concepts which are the weighted sums of the questions in their section: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. Each scale is transformed into a 0 (minimum) to 100 (maximum) scale on the assumption each question carries equal weight. These concepts were also summarized into 2 summary scores; Physical Component Summary and Mental Component Summary (both a 0-100 scale). The 8 subscales, 2 summary scores and transition Question 2 (TR Scale, measured on a scale of 1 \[minimum\] to 5 \[maximum\]) were subjected to analysis. Higher domain, summary scores, and TR scale scores indicate better health status. Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. First-order autoregressive variance-covariance structure was used.
Least Squares Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36 Months 24, 36 ESRD-SCL: a 43-item disease specific self-administered questionnaire. Participants' rated the question "At the moment,how much do you suffer?" for each item on a 5 point scale, range (Ra) from 0 (not at all) to 4 (extremely). Consisted of 6 subscales: Cardiac and Renal (CR) dysfunction; Ra 0 to 28, Increased(In) Growth of Gum and Hair (IGGH); Ra 0 to 20, Limited Cognitive Capacity (LCC); Ra 0 to 32, Limited Physical Capacity (LPC); Ra 0 to 40, Side Effects (SEs) of Corticosteroids; Ra 0 to 20, Transplantation Associated Psychological Distress (TAPD); Ra 0 to 32. Total Score: 0 to 172, higher scores indicate greater dysfunction.
Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.Least Squares Means of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36 Months 24, 36 SODA:17-item health scale, assessed participant-reported perceptions of dyspepsia; consists of 3 subscales: Pain Intensity (PI, 6-items to assess pain and intensity of abdominal discomfort; Range: 2 to 47, higher score indicates greater pain and abdominal discomfort), Non-Pain Symptoms (NPS, 7-items to assess severity and impact of non-pain symptoms: burping/belching, heartburn, bloating, flatulence, sour taste, nausea, and bad breath; Range: 7 to 35, higher scores indicate increased symptom severity and influence), and Satisfaction (4-items to assess degree of satisfaction with abdominal discomfort; Range: 2 to 23, higher scores indicate more satisfaction).
Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.Mean Trough Levels of Tofacitinib by Visit Months 18 and 24 (-2 hours, predose, 1 hour, 2 hours), Month 30 (predose, 1 hour and 2 hours), Month 36 (predose, 1, 2, and 4 hours), Months 42, 48, 54, 60, 66, 72 (predose and 2 hours) The dates and times were recorded for the 6 doses of tofacitinib administered before each scheduled pharmacokinetic (PK) sampling. The participant was instructed to follow a 12 hourly schedule for these 6 doses of tofacitinib, with each dose administered within 1 hour of the scheduled time. Trough samples were collected 0 to 10 minutes prior to the morning dose. 1 hour postdose samples were required within 10 minutes of the nominal time point. Samples taken at -2 hours predose and at time points \>1 hour post dose were required within 30 minutes of the nominal time point.
Trial Locations
- Locations (64)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
NUCATS's Clinical Research Unit
🇺🇸Chicago, Illinois, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
California Institute of Renal Research
🇺🇸San Diego, California, United States
Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Dallas Transplant Institute
🇺🇸Dallas, Texas, United States
Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
California Pacific Medical Center - Pacific Campus
🇺🇸San Francisco, California, United States
UCSF Medical Center - Long Hospital
🇺🇸San Francisco, California, United States
USCF Medical Center - Connie Frank Transplant Center
🇺🇸San Francisco, California, United States
Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Hospital Curry Cabral
🇵🇹Lisboa, Portugal
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Hospitais da Universidade de Coimbra, EPE
🇵🇹Coimbra, Portugal
Cedars-Sinai MedicalCenter
🇺🇸Los Angeles, California, United States
Balboa Institute of Transplantation
🇺🇸San Diego, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University Of Florida
🇺🇸Gainesville, Florida, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Drexel University College of Medicine - Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Westmead Hospital, Department of Renal Medicine
🇦🇺Westmead, New South Wales, Australia
Central Northern Adelaide Renal and Transplantation Service
🇦🇺Adelaide, South Australia, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Hopital Erasme
🇧🇪Anderlecht, Brussels, Belgium
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital do Rim e Hipertensao
🇧🇷Sao Paulo, Brazil
Ambulatorio Pos Transplante do Hospital do Rim a Hipertensao
🇧🇷Sao Paulo, SP, Brazil
Hopital Necker
🇫🇷Paris Cedex 15, France
Institut Klinicke a Experimentalni Mediciny
🇨🇿Praha 4 Krc, Czechia
CHRU de Nancy-Brabois - Service de Nephrologie
🇫🇷Vandoeuvre Les Nancy, France
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Istituto di Clinica Chirurgica, Universita Cattolica del Sacro Cuore
🇮🇹Roma, RM, Italy
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Hospital Universitari de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Oslo universitetssykehus HF- Rikshospitalet
🇳🇴Oslo, Norway
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Stanford School of Medicine
🇺🇸Palo Alto, California, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Department of Surgery, Yonsei University College of Medicine Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center, Department of Surgery
🇰🇷Seoul, Korea, Republic of
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
UNC Department of Surgery, Clinical Trials Consortium
🇺🇸Chapel Hill, North Carolina, United States
UNC Department of Surgery/Abdominal Transplant Division
🇺🇸Chapel Hill, North Carolina, United States
University of North Carolina, Department of Medicine/Nephrology
🇺🇸Chapel Hill, North Carolina, United States
Nephrology Clinic
🇺🇸Charleston, South Carolina, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Investigational Drug Services (IDS) / UNC Healthcare
🇺🇸Chapel Hill, North Carolina, United States
Division of Pharmacotherapy, School of Pharmacy, University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Yale Physicians Building
🇺🇸New Haven, Connecticut, United States
Transplant Clinic/UNC Heathcare
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina, Department of Transplantation Surgery
🇺🇸Charleston, South Carolina, United States