Renal Transplantation
Conditions
Keywords
belatacept, rabbit antithymocyte globulin, alemtuzumab, corticosteroid withdrawal
Brief summary
The study purpose is to determine the safety and efficacy of a belatacept-based immunosuppressive regimen (calcineurin inhibitor free) with alemtuzumab or rabbit antithymocyte globulin (rATG) induction and early glucocorticoid withdrawal (CSWD) and a belatacept-based immunosuppressive regimen with tacrolimus-based regimen with rabbit antithymocyte globulin induction and early glucocorticoid withdrawal in renal transplant recipients. The hypothesis is that a belatacept-based immunosuppressive regimen with alemtuzumab induction, mycophenolate mofetil (MMF)/mycophenolic acid (MPA), and early glucocorticoid withdrawal (Group A) in renal transplant recipients or Belatacept-based immunosuppressive regimen with rabbit antithymocyte globulin induction, MMF/MPA and early glucocorticoid withdrawal (Group B) will lead to less risk of graft loss, patient death, or reduced renal function at 12 months as compared to a tacrolimus-based immunosuppressive regimen with rabbit antithymocyte globulin, MMF/MPA, and early glucocorticoid withdrawal in renal transplant recipients (Group C).
Detailed description
Renal transplant is the most effective treatment for end-stage renal disease. It provides improved survival and quality of life. Maintenance of a functioning renal transplant mandates lifelong immunosuppressive therapy to prevent immune destruction of the graft. Current immunosuppressive regimens yield 1-year survival rates of 89% for cadaveric and 94% for living-donor grafts. Over time, however, there is progressive loss of both subjects and grafts. Five-year graft survival for cadaveric and living related donor renal transplants is 67% and 80%, respectively. The most common causes of long-term subject and graft loss in kidney transplant recipients are cardiovascular disease and chronic allograft nephropathy (CAN), respectively. Paradoxically, the principal immunosuppressive therapies for renal transplant, the calcineurin inhibitors (CNIs), cyclosporine (CsA) and tacrolimus, directly contribute to long-term allograft loss and subject death, since they are inherently nephrotoxic and can cause or exacerbate cardiovascular risks including hypertension, hypercholesterolemia, and diabetes mellitus. There is, therefore, a substantial unmet medical need for new therapies in renal transplant that can provide short-term subject and graft survival comparable to the CNIs without their long-term nephrotoxic, cardiovascular, and metabolic effects. Because belatacept can be administered at the time of engraftment rather than in a delayed fashion, as is frequently necessary with CNIs - especially in those allografts with initial impaired renal function-- it affords immunosuppression in a timely manner. Unlike CNIs, the targeted mechanism of action of belatacept should provide immunosuppression without nephrotoxicity or adverse effects on the cardiovascular/metabolic profile. Glucocorticoids have been a cornerstone of immunosuppressive therapy for six decades. Although glucocorticoids provide potent suppression of allo-immune responses in humans, their adverse effects including infection, diabetes, weight gain, hypertension, hyperlipidemia, bone disease, dermal thinning, collagen loss in multiple tissues, and cataracts, combined with a lack of available therapeutic monitoring all argue against their continued use in transplantation. Belatacept represents a potential new treatment option for renal transplant recipients, which addresses the current unmet need for an immunosuppressive treatment that provides short-term outcomes comparable to calcineurin inhibitors (CNIs) with the potential to avoid their renal, cardiovascular, and metabolic toxicities. However, the initial Phase 3 studies exhibited in higher rate of acute rejection and malignancy. The malignancies were associated with recipients who were EBV negative at the time of transplant. All EBV negative patients are precluded from treatment with Belatacept. Due to the limitations of Phase 3 trial designs and the required use of basilixumab induction, it is intuitive that the addition of a potent t cell depleting induction agent may decrease the overall acute rejection rate in patients treated with belatacept. The current study tests these assumptions with the following immunosuppressive regimens. Group A and B consist of potent T-cell depleting induction agents combined with belatacept. Group C represents the most common immunosuppressive regimen currently utilized in the United States. Each of these regimens include early withdrawal of glucocorticoids along with maintenance mycophenolate mofetil. Based upon the totality of available evidence, the current study offers a favorable benefit/risk profile to study subjects, and the potential to continue to provide important data for the development of new immunosuppressive regimens that address important unmet needs. The proposed Phase 4 study is designed to determine whether belatacept, in combination with other immunosuppressive agents (rabbit antithymocyte globulin or alemtuzumab, mycophenolate mofetil/EC mycophenolate sodium), may provide acceptable efficacy and safety in de novo kidney transplant recipients, in a regimen that provides simultaneous CNI freedom and early CSWD.
Interventions
DRUGAlemtuzumab
Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.
Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
DRUGBelatacept
Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is defined as the day of transplant.
DRUGTacrolimus
Tacrolimus will be administered orally twice daily (BID). The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally. Tacrolimus should be started post-transplant within 48 hours or when serum creatinine drops lower than 4mg/dL, whichever comes first. The initial targeted trough level of tacrolimus will be 8 - 12 ng/mL for Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter.
DRUGMycophenolate mofetil
The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).
DRUGearly cessation of steroids
Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below: Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids
Sponsors
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients \> 18 years of age. 2. Patient who is receiving a renal transplant from a living or deceased donor. 3. Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion. 4. The patient has given written informed consent to participate in the study.
Exclusion criteria
1. Patient has previously received an organ transplant other than a kidney. 2. Patient is receiving an human leucocyte antigen (HLA) identical living donor transplant. 3. Patient who is a recipient of a multiple organ transplant. 4. Patient has a most recent cytotoxic panel reactive antibody (PRA) of \>25% or calculated PRA of \> 50% where multiple moderate level HLA antibodies exist and in the opinion of the PI represents substantial HLA sensitization. 5. Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies. 6. Patient with a donor specific antibody (DSA) as deemed by the local PI to be associated with significant risk of rejection. 7. Patient has received a blood group (ABO) incompatible donor kidney. 8. The donor and/or donor kidney meet any of the following extended criteria for organ donation (ECD): * Donor age \>/= 60 years OR * Donor age 50-59 years and 1 of the following: * Cerebrovascular accident (CVA) + hypertension + serum creatinine (SCr) \> 1.5 mg/dL OR * CVA + hypertension OR * CVA + SCr \> 1.5 mg/dL OR * Hypertension + SCr \> 1.5 mg/dL OR * Cold ischemia time (CIT) \> 24 hours, donor age \> 10 years OR * Donation after cardiac death (DCD) 9. Recipients will be receiving a dual or en bloc kidney transplant. 10. Donor anticipated cold ischemia is \> 30 hours. 11. Recipient that is seropositive for hepatitis C virus (HCV) with detectable Hepatitis C viral load are excluded. HCV seropositive patients with a negative HCV viral load testing may be included. 12. Recipients who are Hepatitis B core antibody seropositive are eligible if their hepatitis B viral loads are negative. After transplant, their hepatitis B viral loads will be monitored every three months for the first year after transplant. If hepatitis B viral loads become positive, patients will be treated per institutional standard of care. 13. Patients who are Hepatitis B surface antibody seropositive and who receive a kidney from a Hepatitis B core surface antibody positive donor may be included. 14. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV). 15. Recipient who is seronegative for Epstein Barr virus (EBV). 16. Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives. 17. Patients with thrombocytopenia (PLT \< 75,000/mm3), and/or leucopoenia (WBC \< 2,000/mm3), or anemia (hemoglobin \< 6 g/dL) prior to study inclusion. 18. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant. 19. Patient who has undergone desensitization therapy within 6 months prior to transplant. 20. Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids. 21. Patient is receiving chronic steroid therapy at the time of transplant. 22. Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years, unless they have an expected disease free survival of \> 95%. 23. Patient is pregnant, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test. 24. Women of childbearing potential must use reliable contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. 25. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator. 26. Inability to cooperate or communicate with the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min | 12 months | Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) \< 45 mL/min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months | 24 months | Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR \< 45 ml/min/1.73m2 |
| eGFR (MRDRD) < 45 ml/Min/1.73m2 | 24 months | Patients with reduced Renal function measured by estimated GFR MDRD \< 45 ml/min at 24 months |
| Biopsy Proven Acute Rejection | 24 months | Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent. |
| Biopsy Proven Acute Cellular Rejection | 24 months | Biopsy proven acute cellular rejection (BPACR) |
| Biopsy Proven Acute Antibody Mediated Rejection | 24 months | Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR) |
| Biopsy Proven Mixed Acute Rejection | 24 months | Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection |
| # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant | 24 months | Number of patients (%) with development of denovo DSA after transplant |
| Mean eGFR (MDRD) (ml/Min/1.73m2) | 24 months | Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint |
| Proteinuria UPC Ratio > 0.8 | 24 months | Number of Patients with a Urine protein/creatinine (UPC) ratio \> 0.8 |
| Patient Death | 24 months | Number of Patients who experienced death, all causes |
| # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss) | 24 months | Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to First BPAR | 24 months | Mean Time to first episode of BPAR (days) |
| # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade | 24 months | Number of patients with their First BPACR with a Banff grade \>= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3. |
| Delayed Graft Function | 24 months | Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant. |
| Leukopenia (WBC < 2000/mm3) | 24 months | Number of patients developing leukopenia defined as WBC \< 2000/mm3 |
| Steroid Therapy | 24 months | Number of patients on treatment with corticosteroids at 2 years |
| Discontinuation of Mycophenolate | 24 months | Number of patients who were discontinued from mycophenolate treatment at 2 years |
| Discontinuation of Study Treatment (Belatacept or Tacrolimus) | 24 months | Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years |
| New Onset Diabetes After Transplantation (NODAT) | 24 months | Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included |
| Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR) | 24 months | Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant. | 107 |
| Group B Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label | 104 |
| Group C Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
Tacrolimus: Tacrolimus will be administered orally twice daily (BID). | 105 |
| Total | 316 |
Baseline characteristics
| Characteristic | Group C | Group B | Total | Group A |
|---|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 12.3 | 51.6 years STANDARD_DEVIATION 11.7 | 51.4 years STANDARD_DEVIATION 12.1 | 51.1 years STANDARD_DEVIATION 13.1 |
| calculated panel reactive antibody (cPRA) % | 5.9 percentage STANDARD_DEVIATION 15.7 | 6.4 percentage STANDARD_DEVIATION 16.4 | 5.8 percentage STANDARD_DEVIATION 14.6 | 4.9 percentage STANDARD_DEVIATION 12.7 |
| Cytomegalovirus (CMV) High Risk status (D+/R-) | 25 Participants | 21 Participants | 64 Participants | 18 Participants |
| Deceased donor | 25 Participants | 26 Participants | 78 Participants | 27 Participants |
| Living related donor | 33 Participants | 25 Participants | 83 Participants | 25 Participants |
| Living unrelated donor | 47 Participants | 53 Participants | 155 Participants | 55 Participants |
| # Patients with Pre-existing Donor Specific Antibody (DSA) | 1 Participants | 4 Participants | 6 Participants | 1 Participants |
| Pre-emptive transplant | 40 Participants | 27 Participants | 104 Participants | 37 Participants |
| Pre-existing diabetes mellitus | 33 Participants | 33 Participants | 92 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 11 Participants | 42 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) White | 80 Participants | 88 Participants | 250 Participants | 82 Participants |
| Region of Enrollment United States | 105 participants | 104 participants | 316 participants | 107 participants |
| Repeat Transplant | 3 Participants | 2 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 36 Participants | 38 Participants | 104 Participants | 30 Participants |
| Sex: Female, Male Male | 69 Participants | 66 Participants | 212 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 107 | 4 / 104 | 1 / 105 |
| other Total, other adverse events | 91 / 107 | 90 / 104 | 92 / 105 |
| serious Total, serious adverse events | 58 / 107 | 66 / 104 | 62 / 105 |
Outcome results
Primary
# Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min
Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) \< 45 mL/min
Time frame: 12 months
Population: Intent to treat analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min | 9 Participants |
| Group B | # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min | 15 Participants |
| Group C | # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min | 14 Participants |
Secondary
Biopsy Proven Acute Antibody Mediated Rejection
Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Biopsy Proven Acute Antibody Mediated Rejection | 2 Participants |
| Group B | Biopsy Proven Acute Antibody Mediated Rejection | 2 Participants |
| Group C | Biopsy Proven Acute Antibody Mediated Rejection | 3 Participants |
Secondary
Biopsy Proven Acute Cellular Rejection
Biopsy proven acute cellular rejection (BPACR)
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Biopsy Proven Acute Cellular Rejection | 14 Participants |
| Group B | Biopsy Proven Acute Cellular Rejection | 22 Participants |
| Group C | Biopsy Proven Acute Cellular Rejection | 2 Participants |
Secondary
Biopsy Proven Acute Rejection
Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Biopsy Proven Acute Rejection | 20 Participants |
| Group B | Biopsy Proven Acute Rejection | 26 Participants |
| Group C | Biopsy Proven Acute Rejection | 7 Participants |
Secondary
Biopsy Proven Mixed Acute Rejection
Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Biopsy Proven Mixed Acute Rejection | 4 Participants |
| Group B | Biopsy Proven Mixed Acute Rejection | 2 Participants |
| Group C | Biopsy Proven Mixed Acute Rejection | 2 Participants |
Secondary
eGFR (MRDRD) < 45 ml/Min/1.73m2
Patients with reduced Renal function measured by estimated GFR MDRD \< 45 ml/min at 24 months
Time frame: 24 months
Population: Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | eGFR (MRDRD) < 45 ml/Min/1.73m2 | 9 Participants |
| Group B | eGFR (MRDRD) < 45 ml/Min/1.73m2 | 8 Participants |
| Group C | eGFR (MRDRD) < 45 ml/Min/1.73m2 | 20 Participants |
Secondary
Mean eGFR (MDRD) (ml/Min/1.73m2)
Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Mean eGFR (MDRD) (ml/Min/1.73m2) | 65.5 ml/min/1.73m2 | Standard Deviation 18.9 |
| Group B | Mean eGFR (MDRD) (ml/Min/1.73m2) | 65.3 ml/min/1.73m2 | Standard Deviation 19.3 |
| Group C | Mean eGFR (MDRD) (ml/Min/1.73m2) | 63.4 ml/min/1.73m2 | Standard Deviation 19.8 |
Secondary
# of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant
Number of patients (%) with development of denovo DSA after transplant
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant | 5 Participants |
| Group B | # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant | 1 Participants |
| Group C | # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant | 5 Participants |
Secondary
Patient Death
Number of Patients who experienced death, all causes
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Patient Death | 2 Participants |
| Group B | Patient Death | 4 Participants |
| Group C | Patient Death | 1 Participants |
Secondary
# Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)
Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss) | 0 Participants |
| Group B | # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss) | 1 Participants |
| Group C | # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss) | 1 Participants |
Secondary
# Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months
Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR \< 45 ml/min/1.73m2
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months | 11 Participants |
| Group B | # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months | 13 Participants |
| Group C | # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months | 21 Participants |
Secondary
Proteinuria UPC Ratio > 0.8
Number of Patients with a Urine protein/creatinine (UPC) ratio \> 0.8
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Proteinuria UPC Ratio > 0.8 | 11 Participants |
| Group B | Proteinuria UPC Ratio > 0.8 | 5 Participants |
| Group C | Proteinuria UPC Ratio > 0.8 | 21 Participants |
Other Pre-specified
Delayed Graft Function
Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Delayed Graft Function | 3 Participants |
| Group B | Delayed Graft Function | 1 Participants |
| Group C | Delayed Graft Function | 5 Participants |
Other Pre-specified
Discontinuation of Mycophenolate
Number of patients who were discontinued from mycophenolate treatment at 2 years
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Discontinuation of Mycophenolate | 11 Participants |
| Group B | Discontinuation of Mycophenolate | 9 Participants |
| Group C | Discontinuation of Mycophenolate | 13 Participants |
Other Pre-specified
Discontinuation of Study Treatment (Belatacept or Tacrolimus)
Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Discontinuation of Study Treatment (Belatacept or Tacrolimus) | 11 Participants |
| Group B | Discontinuation of Study Treatment (Belatacept or Tacrolimus) | 9 Participants |
| Group C | Discontinuation of Study Treatment (Belatacept or Tacrolimus) | 5 Participants |
Other Pre-specified
Leukopenia (WBC < 2000/mm3)
Number of patients developing leukopenia defined as WBC \< 2000/mm3
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Leukopenia (WBC < 2000/mm3) | 22 Participants |
| Group B | Leukopenia (WBC < 2000/mm3) | 14 Participants |
| Group C | Leukopenia (WBC < 2000/mm3) | 15 Participants |
Other Pre-specified
New Onset Diabetes After Transplantation (NODAT)
Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | New Onset Diabetes After Transplantation (NODAT) | 11 Participants |
| Group B | New Onset Diabetes After Transplantation (NODAT) | 5 Participants |
| Group C | New Onset Diabetes After Transplantation (NODAT) | 12 Participants |
Other Pre-specified
# Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade
Number of patients with their First BPACR with a Banff grade \>= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade | 5 Participants |
| Group B | # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade | 12 Participants |
| Group C | # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade | 0 Participants |
Other Pre-specified
Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)
Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR) | 8 Participants |
| Group B | Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR) | 15 Participants |
| Group C | Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR) | 0 Participants |
Other Pre-specified
Steroid Therapy
Number of patients on treatment with corticosteroids at 2 years
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Steroid Therapy | 16 Participants |
| Group B | Steroid Therapy | 14 Participants |
| Group C | Steroid Therapy | 9 Participants |
Other Pre-specified
Time to First BPAR
Mean Time to first episode of BPAR (days)
Time frame: 24 months
Population: Intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Time to First BPAR | 229 days | Standard Deviation 147.7 |
| Group B | Time to First BPAR | 131.6 days | Standard Deviation 119.6 |
| Group C | Time to First BPAR | 159.6 days | Standard Deviation 219.6 |