Belatacept Regimen for Kidney Transplant Recipients
Recruiting in Palo Alto (17 mi)
+50 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Bristol-Myers Squibb
Must be taking: Calcineurin inhibitors
Must not be taking: Rituximab, Plasmapheresis
Disqualifiers: EBV negative, Acute rejection, TB, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the benefits and risks of conversion of existing adolescent kidney allograft recipients aged 12 to less than 18 years of age to a belatacept-based immunosuppressive regimen as compared to continuation of a calcineurin inhibitor-based regimen and their adherence to immunosuppressive medications.
Will I have to stop taking my current medications?
The trial involves switching from a calcineurin inhibitor-based regimen to a belatacept-based regimen, so you may need to stop or change your current medications. The protocol does not specify a washout period, but you should discuss this with the trial team.
What data supports the effectiveness of the drug regimen for kidney transplant recipients?
Research shows that the extended-release formulation of tacrolimus (Advagraf/Astagraf XL) used with mycophenolate mofetil (CellCept) provides similar patient and graft survival rates compared to the immediate-release version (Prograf). Additionally, using enteric-coated mycophenolate sodium (Myfortic) with tacrolimus has been shown to be effective and safe, with high patient and graft survival rates in kidney transplant recipients.
12345Is Belatacept safe for kidney transplant recipients?
Belatacept is generally considered safe for kidney transplant recipients, but it is not recommended for those who are Epstein-Barr virus seronegative due to a higher risk of developing a type of cancer called posttransplant lymphoproliferative disorder. Some studies have shown a higher rate of acute rejection episodes with Belatacept, and a trial was stopped early due to serious adverse events, so risks and benefits should be carefully considered.
678910How is the drug Belatacept different from other treatments for kidney transplant recipients?
Belatacept is unique because it is a biological agent used for primary maintenance immunosuppression in kidney transplant patients, allowing for the reduction or withdrawal of calcineurin inhibitors (CNIs) and steroids, which can have harmful side effects. Unlike traditional treatments, Belatacept is administered intravenously and does not require plasma concentration monitoring, although it is less convenient than oral medications.
68111213Eligibility Criteria
This trial is for adolescents aged 12 to <18 who have had a kidney transplant at least 6 months ago, are vaccinated against SARS-CoV-2, and show no current EBV infection. They must be on a stable calcineurin inhibitor regimen with mycophenolate and possibly corticosteroids. Those previously treated with belatacept or having certain rejection episodes or TB can't participate.Inclusion Criteria
I've been on a stable medication regimen for my condition for at least 30 days.
I received a kidney transplant more than 6 months ago.
My kidney function has been stable for the last 3 months.
+3 more
Exclusion Criteria
I have been treated for acute rejection of a transplant within the last 6 months.
I have had a severe rejection episode with my current organ transplant.
I have been treated with belatacept or was in a belatacept trial with my current transplant.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants are converted from a calcineurin inhibitor-based regimen to a belatacept-based regimen or continue with the calcineurin inhibitor-based regimen
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study compares the effects of switching adolescent kidney transplant recipients from their current calcineurin inhibitor-based treatment (like Tacrolimus) to a Belatacept-based regimen versus continuing their existing treatment. It also looks at how well they stick to their medication schedules.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlapExperimental Treatment6 Interventions
Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI)
Group II: Arm 2: Continue calcineurin inhibitor-based regimenActive Control5 Interventions
Belatacept is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Nulojix for:
- Prophylaxis of organ rejection in adult patients receiving a kidney transplant
🇪🇺 Approved in European Union as Nulojix for:
- Prophylaxis of organ rejection in adult patients receiving a kidney transplant
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at Birmingham - School of MedicineBirmingham, AL
UCLA Clinical & Translational Research Center (CTRC)-PediatricsLos Angeles, CA
Cleveland Clinic-Children's Hospital Pediatric Research InstituteCleveland, OH
Cincinnati Children's Hospital Medical Center-NephrologyCincinnati, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Bristol-Myers SquibbLead Sponsor
References
Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. [2021]Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed. Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients' adherence to treatment.
A 6-month, open-label, multicenter clinical study in Korean de novo renal transplant patients evaluating the efficacy, safety, and tolerance of myfortic concomitantly used with tacrolimus. [2022]Enteric-coated mycophenolate sodium (myfortic, Novartis Pharma AG, Basel, Switzerland) is designed to improve the gastrointestinal tolerability of micophenolic acid. This study was designed to evaluate the efficacy and safety of myfortic in Korean de novo renal transplantation. A total of 65 patients from four transplantation centers received the study drug at least once and were included in the intention-to-treat analysis. This study was an open-label, single-arm, multicenter trial with 6-month patient follow-up. Patients received 360 mg (body weight 50 kg) of myfortic per day with tacrolimus and steroids. Induction therapy included basiliximab. The incidence of biopsy-confirmed acute rejection (primary endpoint) within 6 months after transplantation was 7/65 (10.8%). There were 2 (3.1%) graft losses due to severe acute rejection and 1 (1.5%) patient-death due to cardiac arrest. Twenty-two (38.8%) patients experienced gastrointestinal discomfort; however, only 3 (4.5%) cases were associated with an apparent drug reaction. Seventeen (25.4%) patients underwent dose adjustment or myfortic discontinuation during the study period. Patient and graft survival rates at 6 months posttransplantation were 98.1% and 97.0%. Myfortic with tacrolimus-based immunosuppression was efficient and safe after de novo renal transplantation in Korean patients.
Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients. [2021]In a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported.
Safety assessment of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable renal transplant recipients. [2016]The immunosuppressant mycophenolate mofetil (MMF; CellCept) has greatly improved transplant recipients' clinical outcomes, but its efficacy may be limited by dose adjustments due to adverse events (AEs). An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic), designed to improve gastrointestinal tolerability is now available. This Latin-American, prospective, multicenter, open-label, 6-month trial assessed the safety and tolerability of converting renal transplant recipients from MMF to EC-MPS. In total, 237 renal transplant recipients (stable > or = 3 months' posttransplant) receiving MMF (
Enteric-coated mycophenolate sodium given in combination with tacrolimus has a lower incidence of serious infections in Asian renal-transplant recipients compared with mycophenolate mofetil. [2016]To compare the characteristics of the enteric-coated formulation of mycophenolate sodium (EC-MPS, myfortic) and mycophenolate mofetil (MMF, CellCept) given in combination with tacrolimus in Asian renal-transplant recipients.
Belatacept utilization recommendations: an expert position. [2015]There is a continuing need for an immunosuppressive therapy that offers a high benefit-risk profile for renal transplant recipients, supporting long-term patient and graft survival while minimizing cumulative nephrotoxicity and other side effects. Belatacept , the first biological agent developed for primary maintenance immunosuppression, was recently approved for use in Europe. Belatacept combined with corticosteroids and a mycophenolic acid is indicated for prophylaxis of graft rejection in adults receiving renal transplant. Its use is contraindicated in Epstein-Barr virus seronegative or serostatus unknown patients due to increased risk of developing posttransplant lymphoproliferative disorder.
Belatacept in kidney transplantation. [2018]In June 2011 the US Food and Drug Administration approved belatacept (Nulojix; Bristol-Myers Squibb, Princeton, New Jersey, USA) for the prophylaxis of organ rejection in adult kidney transplant recipients. This review will discuss the use of belatacept for the prevention of acute rejection as part of a maintenance immunosuppression regimen.
Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. [2020]Belatacept is a novel immunosuppressive therapy designed to improve clinical outcomes associated with kidney transplant recipients while minimizing use of calcineurin inhibitors (CNIs).
Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. [2022]Our aim was to determine the impact of converting from tacrolimus to belatacept in patients with stable low estimated glomerular filtration rate (eGFR) early after kidney transplant.
Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. [2023]The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.
Belatacept. [2019]Immunosuppressive therapy designed to prevent kidney graft rejection usually consists of a triple-drug combination including a corticosteroid, a calcineurin inhibitor (ciclosporin or tacrolimus) and a drug that inhibits cell proliferation (azathioprine or mycophenolate mofetil). Belatacept is closely related to abatacept, an immunosuppressant marketed for rheumatic diseases. It is now authorised in the European Union for the prevention of kidney graft rejection, as a replacement for the calcineurin inhibitor. Two randomised controlled trials compared belatacept (2 doses) versus ciclosporin as part of the immunosuppressive regimen in respectively 666 and 534 patients. After 3 years of follow-up, survival with a functioning graft did not differ between the groups (about 80% in the trial closest to European protocols). Only the use of a high dose of belatacept instead of ciclosporin resulted in better preservation of renal function, but this is not the authorised dose. Lymphomas, particularly those affecting the central nervous system, were more frequent with belatacept in both trials (1.4% versus 0.9%). The risk was particularly high in patients receiving the high dose of belatacept, and in patients who were seronegative for Epstein-Barr virus. Overall, the risk of infections seems to be similar with belatacept and ciclosporin, but certain severe infections were more frequent with belatacept, including progressive multifocal leukoencephalopathy and tuberculosis. Unlike ciclosporin, belatacept plasma concentrations do not need to be monitored. However, intravenous belatacept administration is less convenient than oral ciclosporin administration, especially during long-term treatment. Overall, it is better to continue to use ciclosporin, a better-documented drug, as part of immunosuppressive therapy after kidney transplantation.
Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. [2023]Belatacept has been demonstrated as an effective alternative immunosuppressant in kidney transplant recipients. This study focuses on outcomes of early and late conversion to Belatacept-based immunosuppression after kidney transplant.
Does belatacept improve outcomes for kidney transplant recipients? A systematic review. [2018]Belatacept was intended to provide better outcomes for kidney transplant (KT) recipients by allowing minimization/withdrawal of calcineurin inhibitors (CNI) and steroids.