A Study to Assess the Safety and Efficacy of Alefacept in Kidney Transplant Recipients
- Conditions
- Kidney Transplantation
- Interventions
- Registration Number
- NCT00543569
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
A study to assess the safety and efficacy of Alefacept in de novo kidney transplant patients.
- Detailed Description
This is a 4 arm (all active) study to determine the safety and efficacy of Alefacept in de novo kidney transplant recipients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
- Subject is anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
- Subject is a recipient of a de novo kidney transplant
- Subject is a recipient of a kidney from a non-human leukocyte antigen (HLA) identical related living donor, a non-related living donor, or a deceased donor
-
Subject has a screening (pre-operative)estimated cluster of differentiation (CD) 4+ T-cell count of < 250 cells/µL
-
Subject will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
-
Recipient has a positive T or B-cell cross match by investigational site's standard method of determination
-
Subject will receive a kidney from a 50-65 year old deceased donor with one of the following:
- History of hypertension and a terminal serum creatinine > 1.5 mg/dL
- Cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
- History of hypertension and cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tacrolimus/MMF/Basiliximab mycophenolate mofetil Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months. Tacrolimus/MMF/Basiliximab Corticosteroids Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus Corticosteroids Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months. Alefacept QOW/Tacrolimus/MMF Corticosteroids Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus/MMF mycophenolate mofetil Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus/MMF Corticosteroids Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months. Tacrolimus/MMF/Basiliximab tacrolimus Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus/MMF Alefacept Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus/MMF tacrolimus Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus tacrolimus Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months. Alefacept QOW/Tacrolimus/MMF tacrolimus Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months. Alefacept QOW/Tacrolimus/MMF mycophenolate mofetil Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months. Tacrolimus/MMF/Basiliximab basiliximab Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months. Alefacept QW/Tacrolimus Alefacept Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months. Alefacept QOW/Tacrolimus/MMF Alefacept Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Biopsy-confirmed Acute Rejection (BCAR) at Month 6 Assessed by Local Review 6 months Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.
The Kaplan-Meier estimates at Day 182 was used for the analyses at 6 months. Lost to follow-up or patients with missing outcomes were censored at their last follow up visit.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With BCAR at Month 12 Assessed by Local Review 12 months Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.
The Kaplan-Meier estimates at Day 365 was used for the analyses at 12 months. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Graft Survival at Month 6 and Month 12 6 months and 12 months Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months and 12 months after the skin closure date. Graft loss was defined as patient death, retransplant, permanent return to dialysis (dialysis greater than 30 days) or transplant nephrectomy.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Time to First T-cell Mediated BCAR Assessed by Central Review 12 months The time to first T-cell mediated BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a T-cell mediated BCAR are included in the analysis.
Percentage of Participants With Anti-lymphocyte-treated Rejection at Months 6 and 12 6 months and 12 months Participants with histologically proved Banff Grade II or III rejection could receive anti-rejection therapy with anti-lymphocyte antibodies per institutional protocol.
The use of anti-lymphocyte antibody therapy at any time during a suspected or proven rejection episode for the treatment of acute rejection was considered an event.Percentage of Participants With Multiple Rejection Episodes at Months 6 and 12 6 months and 12 months All participants were evaluated for the incidence of multiple rejection episodes (clinically treated and/or BCAR as assessed by the local reviewer) through 6 months and 12 months.
Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Local Review 6 months and 12 months Efficacy failure is defined as death, graft failure (permanent return to dialysis \[\>30 days\] or retransplant), BCAR according to local review, or lost to follow-up.
Time to First BCAR Assessed by Central Review 12 months The time to first BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.
Maximum Grade of T-cell Mediated Rejection Assessed by Local Review 6 months and 12 months The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.
Grade IA: Cases with significant interstitial infiltration (\> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (\> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising \>25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.Patient Survival at Month 6 and Month 12 6 months and 12 months Patient survival is any participant who is known to be alive 6 months and 12 months after the skin closure date.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Change From Week 4 in Serum Creatinine at Month 6 and 12 Week 4 and Month 6 and 12 Time to First BCAR Assessed by Local Review 12 months The time to first BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.
Maximum Grade of T-cell Mediated Rejection as Assessed by Central Review 6 months and 12 months The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.
Grade IA: Cases with significant interstitial infiltration (\> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (\> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising \>25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.Gastrointestinal Symptom Rating Scale Scores Over Time Months 1, 3, 6, and 12 The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Symptom Rating Scale Scores (GSRS). The GSRS a 15-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to gastrointestinal symptoms.
Percentage of Participants With BCAR at Month 6 and 12 Assessed by Central Review 6 months and 12 months Rejection episodes were confirmed by biopsy by a central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Change From Week 4 in GFR by Iothalamate Clearance at Month 6 Week 4 and Month 6 The glomerular filtration rate was measured directly using iothalamate clearance.
Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Central Review 6 months and 12 months Efficacy failure is defined as death, graft failure (permanent return to dialysis \[\>30 days\] or retransplant), BCAR according to central review, or lost to follow-up.
Time to First T-cell Mediated BCAR Assessed by Local Review 12 months The time to first T-cell mediated BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1.
Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Local Review 6 months and 12 months Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Central Review 6 months and 12 months Rejection episodes were confirmed by biopsy by the central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.Change From Week 4 in Glomerular Filtration Rate Estimated by the MDRD Method at Month 6 and Month 12 Week 4, Month 6 and Month 12 The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) method.
Percentage of Participants With Clinically Treated Acute Rejection at Month 6 and Month 12 6 months and 12 months Patients who received immunosuppressive medications for the treatment of suspected or BCAR were considered to have a clinically-treated acute rejection.
Percentage of Participants With Treatment Failure at Month 6 and 12 6 months and 12 months Treatment failure was defined as death, graft loss, BCAR (local review), lost to follow-up or early discontinuation of treatment regimen. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.
Gastrointestinal Quality of Life Index Score Over Time Months 1, 3, 6, and 12 The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI) symptom severity score. The GIQLI is a 36-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past 2 weeks on a scale from 0 (all of the time) to 4 (never). Possible overall scores ranged from 0 to 4, with higher scores indicating a better quality of life according to the different symptomatic criteria.
Trial Locations
- Locations (38)
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Methodist University Hospital - Memphis
🇺🇸Memphis, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Southern California - University Hospital
🇺🇸Los Angeles, California, United States
St. Vincent/National Institute of Transplantation
🇺🇸Los Angeles, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
UCSD
🇺🇸San Diego, California, United States
California Institute of Renal Research/Sharp Memorial Hospital
🇺🇸San Diego, California, United States
University of California - San Francisco
🇺🇸San Francisco, California, United States
University of Colorado Health Science Center
🇺🇸Aurora, Colorado, United States
University of Florida, Shands Hospital, Gainesville
🇺🇸Gainesville, Florida, United States
Medical College of Georgia, Augusta
🇺🇸Augusta, Georgia, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Rush - Presbyterian - St. Lukes Medical Center
🇺🇸Chicago, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
University of Maryland Center
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
St. Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Buffalo General Hospital
🇺🇸Buffalo, New York, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mt. Sinai School of Medicine
🇺🇸New York, New York, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
New York Presbyterian Hospital - Cornell
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Legacy Transplant Services
🇺🇸Portland, Oregon, United States
University Hospital of Cleveland
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Pinnacle Health at Harrisburg
🇺🇸Harrisburg, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Methodist Hospital Research Institute of Houston
🇺🇸Houston, Texas, United States
Virginia Commonwealth University School of Medicine
🇺🇸Richmond, Virginia, United States
University of Wisconsin Hospital
🇺🇸Madison, Wisconsin, United States
University of Utah Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States