A Phase 2 interventional study of Belatacept and Sirolimus in Renal Transplant, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 2 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-04-21.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
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rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.
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.
National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.
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Exclusion Criteria:
Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
Drug: Belatacept · Drug: Sirolimus · Drug: Anti-thymocyte globulin · Drug: methylprednisolone
10 mg/kg given intravenously (IV) on transplant (day 1), day 5, and at weeks 2, 4, 8 and 12, then 5 mg/kg IV every 4 weeks
Also known as: LEA29Y, Nulojix
4 mg/day (oral tablet) at transplant (day 1), then dose adjusted to maintain serum trough level of 8-12 ng/mL for at least 1 year
Also known as: Rapamycin, Rapamune
1.5 mg/kg given IV daily on days 1 through 4. Subjects are premedicated with glucocorticoids, acetaminophen 650 mg by mouth, and diphenhydramine 25- 50 mg by mouth prior to each dose.
Also known as: ATG, anti-thymocyte immunoglobulin, Thymoglobulin®
500 mg given IV at transplant (day 1), then given 250 mg IV on day 2 and given 0.5 mg/kg IV or prednisone 0.5 mg/kg given by mouth on days 3 and 4
Also known as: Medrol, glucocorticoid
Acute Rejection at 6-Months
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
Time frame: 6 months post-transplant
Participant Survival at 12 Months Post-Transplant
Time frame: 12 months post-transplant
Acute Rejection at 12-Months
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
Time frame: 12 months post-transplant
Tolerance Induction
Time from transplantation to initiation of sirolimus withdrawal.
Time frame: 48 months
Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks
GFR utilizing clearance of iothalamate. GFR is an index of level of kidney function. A higher value means better kidney function.
Time frame: 24 weeks post-transplant
Graft Survival at 12 Months Post-transplant
Time frame: 12 months post-transplant
Time From Transplant to Acute Rejection
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
Time frame: Transplantation until rejection occurs (participants followed up to four years post-transplantation)
Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection
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
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Proportion of Participants With Post-transplant Infections
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)
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Proportion of Participants With Wound Complications
Time frame: Start of study to end of study
Proportion of Participants With Malignancies
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
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)
Proportion of Participants With Chronic Allograft Nephropathy
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Proportion of Participants With Delayed Graft Function
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Proportion of Participants With Post-transplant Diabetes Mellitus
Time frame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Two centers in the United States enrolled five recipients of non-human leukocyte antigen (HLA)-identical living-donor-related renal transplants between January 2007 and January 2009.
| Milestone | Belatacept |
|---|---|
| Started | 5 |
| Completed | 2 |
| Not completed | 3 |
| Withdrew: Withdrawal by subject | 3 |
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
| Participants | Immunosuppression Withdrawal |
|---|---|
| Acute Rejection at 6-Months | 3 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Participant Survival at 12 Months Post-Transplant | 4 |
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
| Participants | Immunosuppression Withdrawal |
|---|---|
| Acute Rejection at 12-Months | 4 |
Time from transplantation to initiation of sirolimus withdrawal.
| Days | Immunosuppression Withdrawal |
|---|---|
| Tolerance Induction | 391 |
GFR utilizing clearance of iothalamate. GFR is an index of level of kidney function. A higher value means better kidney function.
| mL/min/1.73m^2 | Immunosuppression Withdrawal |
|---|---|
| Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks | 62.0 ± 8.5 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Graft Survival at 12 Months Post-transplant | 4 |
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
| Days | Immunosuppression Withdrawal |
|---|---|
| Time From Transplant to Acute Rejection | 15 ± 95.4 |
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
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection | 0 |
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)
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Post-transplant Infections | 4 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Wound Complications | 0 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Malignancies | 0 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With a Sirolimus Associated Adverse Event | 5 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Chronic Allograft Nephropathy | 0 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Delayed Graft Function | 0 |
| Participants | Immunosuppression Withdrawal |
|---|---|
| Proportion of Participants With Post-transplant Diabetes Mellitus | 1 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Immunosuppression Withdrawal | — | 4/5 (80%) | 5/5 (100%) |
| Event | Immunosuppression Withdrawal |
|---|---|
| Kidney transplant rejectionImmune system disorders | 4/5 |
| LymphoceleBlood and lymphatic system disorders | 1/5 |
| Lung infiltrationRespiratory, thoracic and mediastinal disorders | 1/5 |
| Event | Immunosuppression Withdrawal |
|---|---|
| DiarrhoeaGastrointestinal disorders | 4/5 |
| NauseaGastrointestinal disorders | 4/5 |
| AnaemiaBlood and lymphatic system disorders | 3/5 |
| OedemaGeneral disorders | 3/5 |
| HypomagnesaemiaMetabolism and nutrition disorders | 3/5 |
| LeukopeniaBlood and lymphatic system disorders | 2/5 |
| ConstipationGastrointestinal disorders | 2/5 |
| Mouth ulcerationGastrointestinal disorders | 2/5 |
| PyrexiaGeneral disorders | 2/5 |
| BK virus infectionInfections and infestations | 2/5 |
| Age, Categorical(Participants) | Immunosuppression Withdrawal |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 5 |
| >=65 years | 0 |
| Age, Continuous(years) | Immunosuppression Withdrawal |
|---|---|
| Mean | 50.4 ± 5.9 |
| Sex: Female, Male(Participants) | Immunosuppression Withdrawal |
|---|---|
| Female | 3 |
| Male | 2 |
| Region of Enrollment(participants) | Immunosuppression Withdrawal |
|---|---|
| United States | 5 |
Plan to share: Yes — Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.
The record gives a start of Dec 2006, a primary completion of Feb 2010 and a completion of Feb 2010. It does not say whether these dates are actual or estimated.
Results were first posted in Nov 2011, 1 year 9 months after primary completion.
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This study is terminated, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Abatacept · Sirolimus
National Institute of Allergy and Infectious Diseases (NIAID) →