Belatacept to Prevent Organ Rejection in Kidney Transplant Patients
- Conditions
- Renal Transplant
- Interventions
- Registration Number
- NCT00346151
- Brief Summary
Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had renal (e.g., kidney) transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.
- Detailed Description
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 an immunosuppressive treatment regimen 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.
\*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
- Receiving first renal (e.g., kidney) transplant
- Transplant is from a non-HLA-identical living donor
- Willing to use acceptable forms of contraception
- Positive for anti-human globulin (AHG) or T-cell cross-match with the donor
- Receiving multiple-organ transplant
- History of cancer within the 5 years prior to study entry. Patients who have certain nonmelanoma skin cancers are not excluded
- Human immunodeficiency virus (HIV) infected
- Hepatitis B (HBV) or C (HCV) virus infected
- Other active infections
- Active tuberculosis (TB) infection within the 3 years prior to study entry
- Pregnancy or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Belatacept Anti-thymocyte globulin Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus. Belatacept Sirolimus Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus. Belatacept methylprednisolone Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus. Belatacept Belatacept Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
- Primary Outcome Measures
Name Time Method Acute Rejection at 6-Months 6 months post-transplant 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
- Secondary Outcome Measures
Name Time Method Participant Survival at 12 Months Post-Transplant 12 months post-transplant Acute Rejection at 12-Months 12 months post-transplant 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, 1999Tolerance Induction 48 months Time from transplantation to initiation of sirolimus withdrawal.
Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks 24 weeks post-transplant 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 12 months post-transplant Time From Transplant to Acute Rejection Transplantation until rejection occurs (participants followed up to four years post-transplantation) 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, 1999Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection Participants followed from transplantation until completion of study (up to four years post-transplantation) 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, 1999Proportion of Participants With Post-transplant Infections Participants followed from transplantation until completion of study (up to four years post-transplantation) 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 Start of study to end of study Proportion of Participants With Malignancies Participants followed from transplantation until completion of study (up to four years post-transplantation) Proportion of Participants With a Sirolimus Associated Adverse Event Participants followed from transplantation until completion of study (up to four years post-transplantation) Proportion of Participants With Chronic Allograft Nephropathy Participants followed from transplantation until completion of study (up to four years post-transplantation) Proportion of Participants With Delayed Graft Function Participants followed from transplantation until completion of study (up to four years post-transplantation) Proportion of Participants With Post-transplant Diabetes Mellitus Participants followed from transplantation until completion of study (up to four years post-transplantation)
Trial Locations
- Locations (2)
University of California, San Francisco
🇺🇸San Francisco, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States