Renal TransplantationPhase 4NCT01729494
Belatacept Early Steroid Withdrawal Trial
A Phase 4 study testing Alemtuzumab, rabbit antithymocyte globulin and Belatacept in people with Renal Transplantation, run by University of Cincinnati at 8 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Alemtuzumab, rabbit antithymocyte globulin and Belatacept
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 8 sitesUnited States
- Study dates
- Sep 2012to Dec 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients > 18 years of age.
- Patient who is receiving a renal transplant from a living or deceased donor.
- Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.
- The patient has given written informed consent to participate in the study.
Who cannot join
- Patient has previously received an organ transplant other than a kidney.
- Patient is receiving an human leucocyte antigen (HLA) identical living donor transplant.
- Patient who is a recipient of a multiple organ transplant.
- 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.
- Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies.
- Patient with a donor specific antibody (DSA) as deemed by the local PI to be associated with significant risk of rejection.
Show all 34Show fewer
- Patient has received a blood group (ABO) incompatible donor kidney.
- 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)
- Recipients will be receiving a dual or en bloc kidney transplant.
- Donor anticipated cold ischemia is > 30 hours.
- 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.
- 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.
- 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.
- Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).
- Recipient who is seronegative for Epstein Barr virus (EBV).
- Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
- Patients with thrombocytopenia (PLT < 75,000/mm3), and/or leucopoenia (WBC < 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.
- Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.
- Patient who has undergone desensitization therapy within 6 months prior to transplant.
- Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids.
- Patient is receiving chronic steroid therapy at the time of transplant.
- 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%.
- 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.
- Women of childbearing potential must use reliable contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
- 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.
- Inability to cooperate or communicate with the investigator.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Illinois Medical Center at Chicago
Chicago, Illinois, 60612
The Christ Hospital
Cincinnati, Ohio, 45219
University of Cincinnati
Cincinnati, Ohio, 45219
University of Colorado Denver
Denver, Colorado, 80045
University of Wisconsin-Madison
Madison, Wisconsin, 53792
University of Minnesota
Minneapolis, Minnesota, 55455
California Pacific Medical Center
San Francisco, California, 94107
Tampa General Hospital
Tampa, Florida, 33606
About this study
Official title: Randomized, Open Label, Multicenter Study of Belatacept-based Early Steroid Withdrawal Regimen With Alemtuzumab or rATG Induction Compared to Tacrolimus-based Early Steroid Withdrawal Regimen With rATG Induction in Renal Transplantation
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).
Read the 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.
- Conditions
- Renal Transplantation
- Being tested
- Alemtuzumab, rabbit antithymocyte globulin, Belatacept, Tacrolimus, Mycophenolate mofetil
- Keywords
- belatacept, rabbit antithymocyte globulin, alemtuzumab, corticosteroid withdrawal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called Campath
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 globulinDrug
Also called Thymoglobulin
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.
BelataceptDrug
Also called Nulojix
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.
TacrolimusDrug
Also called Prograf, various
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.
Also called Cellcept, various, Myfortic
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).
early cessation of steroidsDrug
Also called prednisone, various
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
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids Receives: Drug: Alemtuzumab; Drug: Belatacept; Drug: Mycophenolate mofetil; Drug: early cessation of steroids |
| Group B | Experimental | Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids Receives: Drug: rabbit antithymocyte globulin; Drug: Belatacept; Drug: Mycophenolate mofetil; Drug: early cessation of steroids |
| Group C | Active comparator | Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids Receives: Drug: rabbit antithymocyte globulin; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: early cessation of steroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min
Number of Patients who experienced any of the following including patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) < 45 mL/min
Measured: 12 months
Secondary outcomes (11)
Number of Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)
Number of patients who experienced Graft loss, not including (censored) patients who lost graft due to death
Measured: 24 months
Number of 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
Measured: 24 months
eGFR (MRDRD) < 45 ml/Min/1.73m2
Patients with reduced Renal function measured by estimated GFR MDRD < 45 ml/min at 24 months
Measured: 24 months
Biopsy Proven Acute Rejection
Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.
Measured: 24 months
Biopsy Proven Acute Cellular Rejection
Biopsy proven acute cellular rejection (BPACR)
Measured: 24 months
Biopsy Proven Acute Antibody Mediated Rejection
Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)
Measured: 24 months
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
Measured: 24 months
Number of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant
Number of patients (%) with development of denovo DSA after transplant
Measured: 24 months
Mean eGFR (MDRD) (ml/Min/1.73m2)
Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint
Measured: 24 months
Proteinuria UPC Ratio > 0.8
Number of Patients with a Urine protein/creatinine (UPC) ratio > 0.8
Measured: 24 months
Patient Death
Number of Patients who experienced death, all causes
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startSep 2012
- Primary completionDec 2018
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Renal TransplantationStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 316 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, E. Steve Woodle, University of Cincinnati
- Investigators
- E. Steve Woodle, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01729494
- Sponsor's protocol ID
- BEST
- Status last verified
- Aug 2020
- First submitted
- 10 Oct 2012
- Last updated
- 24 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pyatt A, McGowan M, Tanaka R, Miyagawa B, Mizuno T, Shields AR, Christianson A, West-Thielke P, Leone JP, Woodle ES, Kaufman D, Wiseman A, Matas AJ, Vinks AA, Alloway RR. Belatacept Pharmacokinetic Analysis of Belatacept Early Steroid Withdrawal Trial (BEST) to Clinical Outcomes and Compared With Reported BENEFIT and BENEFIT-EXT Pharmacokinetic Analysis. Clin Transplant. 2025 Aug;39(8):e70172. doi: 10.1111/ctr.70172.
PubMed 40704545Kaufman DB, Woodle ES, Shields AR, Leone J, Matas A, Wiseman A, West-Thielke P, Sa T, King EC, Alloway RR; BEST Study Group. Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial. Clin J Am Soc Nephrol. 2021 Sep;16(9):1387-1397. doi: 10.2215/CJN.13100820. Epub 2021 Jul 7.
PubMed 34233921Castro-Rojas CM, Godarova A, Shi T, Hummel SA, Shields A, Tremblay S, Alloway RR, Jordan MB, Woodle ES, Hildeman DA. mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection. Transplantation. 2020 May;104(5):1058-1069. doi: 10.1097/TP.0000000000002917.
PubMed 31415033
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open Label, Multicenter Study of Belatacept-based Early Steroid Withdrawal Regimen With Alemtuzumab or rATG Induction Compared to Tacrolimus-based Early Steroid Withdrawal Regimen With rATG Induction in Renal Transplantation
- ClinicalTrials.gov ID
- NCT01729494
- Acronym / sponsor ID
- BEST
- Conditions
- Renal Transplantation
- Keywords
- belatacept, rabbit antithymocyte globulin, alemtuzumab, corticosteroid withdrawal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 316 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- Sep 2012 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 20 Nov 2012 (estimated)
- Results
- Posted 28 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Alemtuzumab, Drug: Belatacept, Drug: Mycophenolate mofetil, Drug: early cessation of steroidsAlemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids |
| Group B | Experimental | Drug: rabbit antithymocyte globulin, Drug: Belatacept, Drug: Mycophenolate mofetil, Drug: early cessation of steroidsRabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids |
| Group C | Active comparator | Drug: rabbit antithymocyte globulin, Drug: Tacrolimus, Drug: Mycophenolate mofetil, Drug: early cessation of steroidsRabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients > 18 years of age.
- Patient who is receiving a renal transplant from a living or deceased donor.
- Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion.
- The patient has given written informed consent to participate in the study.
Key exclusion criteria (34 listed)
- Patient has previously received an organ transplant other than a kidney.
- Patient is receiving an human leucocyte antigen (HLA) identical living donor transplant.
- Patient who is a recipient of a multiple organ transplant.
- 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.
- Patient with a positive T or B cell crossmatch that is primarily due to HLA antibodies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlemtuzumabAlso: CampathAlemtuzumab 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. | Drug | Group A |
| rabbit antithymocyte globulinAlso: ThymoglobulinRabbit 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. | Drug | Group B, Group C |
| BelataceptAlso: NulojixBelatacept 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. | Drug | Group A, Group B |
| TacrolimusAlso: Prograf, variousTacrolimus 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. | Drug | Group C |
| Mycophenolate mofetilAlso: Cellcept, various, MyforticThe 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). | Drug | Group A, Group B, Group C |
| early cessation of steroidsAlso: prednisone, variousGlucocorticoid 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 | Drug | Group A, Group B, Group C |
Primary outcome
Number of Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min
Time frame: 12 months
Number of Patients who experienced any of the following including patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) < 45 mL/min
11 secondary outcomes
Number of Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)
Time frame: 24 months
Number of Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months
Time frame: 24 months
eGFR (MRDRD) < 45 ml/Min/1.73m2
Time frame: 24 months
Biopsy Proven Acute Rejection
Time frame: 24 months
Biopsy Proven Acute Cellular Rejection
Time frame: 24 months
Biopsy Proven Acute Antibody Mediated Rejection
Time frame: 24 months
Biopsy Proven Mixed Acute Rejection
Time frame: 24 months
Number of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant
Time frame: 24 months
Mean eGFR (MDRD) (ml/Min/1.73m2)
Time frame: 24 months
Proteinuria UPC Ratio > 0.8
Time frame: 24 months
Patient Death
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40704545Pyatt A, McGowan M, Tanaka R, Miyagawa B, Mizuno T, Shields AR, Christianson A, West-Thielke P, Leone JP, Woodle ES, Kaufman D, Wiseman A, Matas AJ, Vinks AA, Alloway RR. Belatacept Pharmacokinetic Analysis of Belatacept Early Steroid Withdrawal Trial (BEST) to Clinical Outcomes and Compared With Reported BENEFIT and BENEFIT-EXT Pharmacokinetic Analysis. Clin Transplant. 2025 Aug;39(8):e70172. doi: 10.1111/ctr.70172.
- Derived from this study: PubMed 34233921Kaufman DB, Woodle ES, Shields AR, Leone J, Matas A, Wiseman A, West-Thielke P, Sa T, King EC, Alloway RR; BEST Study Group. Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial. Clin J Am Soc Nephrol. 2021 Sep;16(9):1387-1397. doi: 10.2215/CJN.13100820. Epub 2021 Jul 7.
- Derived from this study: PubMed 31415033Castro-Rojas CM, Godarova A, Shi T, Hummel SA, Shields A, Tremblay S, Alloway RR, Jordan MB, Woodle ES, Hildeman DA. mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection. Transplantation. 2020 May;104(5):1058-1069. doi: 10.1097/TP.0000000000002917.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E. Steve Woodle, MD principal investigator
University of Cincinnati
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alemtuzumab, rabbit antithymocyte globulin and Belatacept in people with Renal Transplantation, run by University of Cincinnati at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01729494, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.