Belatacept for Immunosuppression in Kidney Transplant Recipients

Recruiting in Palo Alto (17 mi)

Overseen by Cyrus Feizpour, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Belatacept

Must not be taking: Investigational drugs

Disqualifiers: Non-kidney transplants, BK nephropathy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of the study is to identify kidney transplant patients that can be transitioned from multi-drug immunosuppression therapy to Belatacept monotherapy, using cell free DNA and gene expression as markers of immune quiescence. The primary objective will be to determine if donor derived-cell free DNA (AlloSure) can be utilized to facilitate Belatacept monotherapy, and to determine if Belatacept is safe and effective as immunosuppression in kidney transplant recipients. The secondary objective is to determine the utility of AlloMap as a predictor of immune quiescence and tolerance of immunosuppressive de-escalation to Belatacept monotherapy, and to evaluate the performance of iBox in predicting adverse outcomes in patients transitioned to Belatacept monotherapy

Will I have to stop taking my current medications?

The trial aims to transition participants from multiple immunosuppressive drugs to Belatacept alone. This suggests you may need to stop some of your current medications, but the protocol does not specify exactly which ones or if there is a specific period to stop them.

What data supports the effectiveness of the drug Belatacept for kidney transplant recipients?

Belatacept has been shown to improve kidney function and reduce the risk of organ rejection in kidney transplant patients compared to traditional drugs like cyclosporine. It also helps preserve kidney structure and has a better cardiovascular risk profile, although it may increase the risk of certain infections. ^{1 2 3 4 5}

Is Belatacept safe for use in kidney transplant recipients?

Belatacept is generally considered safe for kidney transplant recipients, but about 20% of patients may experience side effects like anemia (low red blood cell count), fever, low white blood cell count, diarrhea, urinary tract infections, headaches, and swelling. It may also increase the risk of certain cancers in patients who are not immune to the Epstein-Barr virus, so these patients are usually not given Belatacept. ^{1 2 3 4 6}

How is the drug Belatacept different from other treatments for kidney transplant recipients?

Belatacept is unique because it is a fusion protein designed to block a specific receptor on T cells, helping to prevent organ rejection without the kidney damage often seen with other drugs like cyclosporine. It also has a better cardiovascular risk profile and lower rates of new-onset diabetes compared to cyclosporine, although it may have a higher risk of certain infections and conditions in some patients. ^{1 2 4 5 7}

Eligibility Criteria

This trial is for adult kidney transplant recipients who have had their new organ for at least 9 months, are on Belatacept or can switch to it, and have stable kidney function. It's not for those with severe liver issues, recent acute rejection episodes, multiple transplants, pregnancy plans during the trial, or current participation in other drug trials.

Inclusion Criteria

I've been on Belatacept for my kidney with stable function for 3 months.

My organ transplant is from a non-identical donor.

My kidney function has been stable for the last 3 months.

Exclusion Criteria

My current kidney transplant is affected by BK virus.

I am not pregnant, breastfeeding, nor planning to become pregnant during the trial.

I have severe liver problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monitoring

Eligible patients are monitored for immune quiescence over a 3-month period

3 months

Monthly clinic visits

Immunosuppression Taper

Sequential withdrawal of immunosuppression medications over a 12-month period to transition to Belatacept monotherapy

12 months

Monthly clinic visits, blood draws for routine monitoring and genetic testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Belatacept (Immunosuppressant)

Trial Overview The study tests if DNA markers can help transition patients from multiple immunosuppressant drugs to just Belatacept. Researchers will see if donor-derived cell-free DNA (AlloSure) and gene expression (AlloMap) predict how well a patient's immune system tolerates this change.

Participant Groups

Group I: Immunosuppression Taper Experimental Treatment 1 Intervention

Patients included in this arm are kidney transplant recipients with stable kidney function currently on or are converting to a Belatacept based immunosuppression regimen. Eligible patients who are deemed immune quiescent after a 3 month monitoring period will undergo sequential withdrawal of immunosuppression medications over a 12 month period from a three drug regimen to a Belatacept only immunosuppression regimen. During the total 15 month period patients will be monitored with monthly clinic visits, blood draws for routine monitoring as well as donor derived cell free DNA and genetic testing through KidneyCare to monitor immune suppression.

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 Nearby Select from list below to view details:

UT Southwestern Medical Center Dallas, TX

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center Lead Sponsor

CareDx Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

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.

2. United States pubmed.ncbi.nlm.nih.gov

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. [2019] Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients.

3. New Zealand pubmed.ncbi.nlm.nih.gov

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).

4. Switzerland pubmed.ncbi.nlm.nih.gov

Belatacept: from rational design to clinical application. [2017] Gradually improved immunosuppression has contributed significantly to the progress achieved in transplantation medicine so far. Nevertheless, current drug regimens are associated with late graft loss--in particular as a result of immunologic damage or drug toxicity--and substantial morbidity. Recently, the costimulation blocker belatacept (marketed under the name Nulojix®) has been approved for immunosuppression in renal transplantation. Belatacept (a mutated version of CTLA4Ig) is a fusion protein rationally designed to block CD28, a critical activating receptor on T cells, by binding and saturating its ligands B7-1 and B7-2. In phase II and III trials, belatacept was compared with cyclosporine (in combination with basiliximab, MMF, and steroids). Advantages observed with belatacept include superior graft function, preservation of renal structure and improved cardiovascular risk profile. Concerns associated with belatacept are a higher frequency of cellular rejection episodes and more post-transplant lymphoproliferative disorder (PTLD) cases especially in EBV seronegative patients, who should be excluded from belatacept-based regimens. Thus, after almost three decades of calcineurin inhibitors as mainstay of immunosuppression, belatacept offers a potential alternative. In this article, we will provide an overview of belatacept's preclinical development and will discuss the available evidence from clinical trials.

5. Netherlands pubmed.ncbi.nlm.nih.gov

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.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. [2023] The development of new immunosuppressive drugs for kidney transplantation resulted both in better short-term outcomes and in decreased metabolic, cardiovascular, and nephrotoxicity risk. Belatacept belongs to a new class of immunosuppressive drugs that selectively inhibits T-cell activation by preventing CD28 activation and by binding its ligands B7-1 and B7-2. The result is an inactivation of costimulatory pathways. A comparative analysis of the BENEFIT and BENEFIT-EXT datasets showed belatacept regimens resulted in better cardiovascular and metabolic risk profiles than did cyclosporin A (CsA) regimens: belatacept likewise outperformed CsA in terms of lower blood pressure and serum lipids and less new onset diabetes after transplantation. About 20% of belatacept-treated patients developed adverse effects which included anemia, pyrexia, neutropenia, diarrhea, urinary tract infection, headache, and peripheral edema. At present, belatacept does not seem to predispose patients to a higher rate of infection than CsA maintenance immunosuppression. The risk of posttransplant lymphoproliferative diseases was higher in Epstein-Barr virus (EBV)-seronegative patients than in EBV-seropositive patients, but the risk may be reduced by use of a less intensive regimen and avoidance of EBV-negative patients and of patients whose pretransplant EBV serology is unknown. Belatacept provides a new option for immunosuppressive therapy in kidney transplantation, but needs further evaluation in terms of the late effects that may derive from prolonged blockage of the costimulatory system and the induction of tolerance status.

7. New Zealand pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. [2016] Belatacept is a second-generation cytotoxic T-lymphocyte-associated antigen-4-Ig fusion protein, which down-regulates T-cell response, and is used in the prophylaxis of organ rejection in adults receiving a kidney transplant. This article reviews the pharmacologic properties of belatacept and its clinical efficacy and tolerability in kidney transplant recipients. In the well designed, phase III trials BENEFIT and BENEFIT-EXT (in patients receiving kidneys from living/standard-criteria or extended-criteria donors, respectively), a belatacept-based treatment regimen was noninferior to a cyclosporine (ciclosporin)-based regimen with regard to patient and graft survival and acute graft rejection rate, and was significantly superior to the cyclosporine-based regimen with regard to the rate of renal impairment (in BENEFIT only), at 12 months. Belatacept-based treatment showed long-term efficacy and remained effective after 2, 3, and 4 years with regard to these endpoints. Belatacept was generally well tolerated in patients with kidney transplants from living, standard-criteria, or extended-criteria donors. The most serious adverse events that have been reported with belatacept treatment are post-transplant lymphoproliferative disorder, other malignancies, and serious infections. At month 12, the incidence of new-onset diabetes mellitus after transplant was significantly lower with belatacept than with cyclosporine, and belatacept recipients had significantly lower blood pressure and a significantly smaller increase in certain lipid levels than cyclosporine recipients.