Belatacept to Prevent Organ Rejection in Kidney Transplant Patients (BESTT)

• Acute Rejection at 6-Months [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: Yes ]

  Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads

  1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
  2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
  
  

• Participant Survival at 12 Months Post-Transplant [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]
  
• Acute Rejection at 12-Months [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]

  Incidence of acute rejection[1] at 12 months post-transplant

  1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
  2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
  
  
• Tolerance Induction [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  Time from transplantation to initiation of sirolimus withdrawal.
  
  
• Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks [ Time Frame: 24 weeks post-transplant ] [ Designated as safety issue: No ]

  GFR utilizing clearance of iothalamate.

  GFR is an index of level of kidney function. A higher value means better kidney function.

  
  
• Graft Survival at 12 Months Post-transplant [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]
  
• Time From Transplant to Acute Rejection [ Time Frame: Transplantation until rejection occurs (participants followed up to four years post-transplantation) ] [ Designated as safety issue: Yes ]

  Time (days) from transplant to occurrence of acute rejection[1]

  1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
  2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
  
  
• Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]

  Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy

  1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
  2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999
  
  
• Proportion of Participants With Post-transplant Infections [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  Proportion of participants who experienced infections post-transplant. Participants were checked for any type of opportunistic infection at all study visits post-transplantation (up to 4 years post-transplantation)
  
  
• Proportion of Participants With Wound Complications [ Time Frame: Start of study to end of study ] [ Designated as safety issue: Yes ]
  
• Proportion of Participants With Malignancies [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  
• Proportion of Participants With a Sirolimus Associated Adverse Event [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  
• Proportion of Participants With Chronic Allograft Nephropathy [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  
• Proportion of Participants With Delayed Graft Function [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  
• Proportion of Participants With Post-transplant Diabetes Mellitus [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  

Drugs that suppress the immune system, have contributed to increased success of transplantation. However, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives; these drugs make patients more susceptible to infection and certain kinds of cancer. Belatacept is an experimental medication that specifically targets immune reactions against transplanted organs and has been shown to be effective in preventing kidney transplant rejection in previous clinical trials. Both thymoglobulin, an antibody, and sirolimus, an anti-rejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. This study will evaluate whether belatacept, along with thymoglobulin and sirolimus, is safe in kidney transplant patients. The study will also evaluate this regimen's potential to allow tapering and eventual discontinuation of all immunosuppressive drugs.

This study will last up to 4 years. At the time of transplant, participants will begin a medication schedule consisting of thymoglobulin, sirolimus, and belatacept. Participants will receive infusions of thymoglobulin on days 1 through 4, and a combination of oral sirolimus (daily) and belatacept infusions at day 5, then weeks 2, 4, 8, and monthly for at least 2 years. Dose reduction of belatacept will occur at 12 weeks post-transplant. At Year 2, eligible participants may choose to begin drug withdrawal or continue study therapy through the end of the study. Study visits will occur weekly for the first two months, then monthly. These visits will include belatacept treatment, general medical assessments, blood and urine collection, and other assessments to determine overall health of the recipient's immune system and kidney transplant and to better understand the way the immune system works in the acceptance or rejection of organ transplants.