Belatacept for Immunosuppression in Kidney Transplant Recipients

Overseen By David Wojciechowski, DO

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

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}

Research Team

David Wojciechowski, DO

Principal Investigator

UT Southwestern Medical Center

Cyrus Feizpour, MD

Principal Investigator

UT Southwestern Medical Center

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.

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

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

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

CareDx

Industry Sponsor

Trials

26

Recruited

15,500+

Findings from Research

Belatacept is an effective immunosuppressant for kidney transplant recipients, showing noninferior patient and allograft survival compared to cyclosporine in Phase 3 trials, with improved kidney function over three years.

While belatacept may offer benefits like better renal function and cardiometabolic health, it carries a risk of higher early rejection rates and potential increased risk of posttransplant lymphoproliferative disease, particularly in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. Wojciechowski, D., Vincenti, F.[2018]

An accurate and precise assay for measuring belatacept serum concentrations was developed, showing a measurement range of 0.9-30 mg/L and high accuracy (91%-99%).

This assay was applied in a pharmacokinetic study involving 5 renal transplant recipients, allowing for the visualization of belatacept concentrations over time, which is crucial for optimizing immunosuppressive therapy post-transplant.

NCBI (Pubmed)

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. Klaasen, RA., Egeland, EJ., Chan, J., et al.[2019]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

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. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

Belatacept, a new immunosuppressant for kidney transplantation, has shown superior graft function and better preservation of renal structure compared to traditional treatments like cyclosporine, based on phase II and III clinical trials.

However, belatacept is associated with a higher risk of cellular rejection and post-transplant lymphoproliferative disorder (PTLD), particularly in patients who are EBV seronegative, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: from rational design to clinical application. Wekerle, T., Grinyó, JM.[2017]

Early conversion to belatacept-based immunosuppression after kidney transplantation significantly improved kidney function, as measured by eGFR, from 26.73 to 45.3 ml/min/1.73 m² within one year, while late conversion showed no significant change.

Both early and late conversion groups had a one-year allograft survival rate of 100%, but early conversion was associated with a higher rate of acute T-cell-mediated rejections, suggesting that the choice of immunosuppressants may influence rejection types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. Moein, M., Dvorai, RH., Li, BW., et al.[2023]

Belatacept, a new immunosuppressive drug for kidney transplantation, shows better cardiovascular and metabolic profiles compared to cyclosporin A, including lower blood pressure and serum lipids, and a reduced risk of new onset diabetes after transplantation.

While about 20% of patients on belatacept experienced adverse effects like anemia and infections, it does not appear to increase the risk of infections compared to cyclosporin A, making it a promising option for immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. Ippoliti, G., D'Armini, AM., Lucioni, M., et al.[2023]

Belatacept is as effective as cyclosporine in preventing organ rejection in kidney transplant patients, with similar rates of patient and graft survival and acute rejection, while showing a significant advantage in reducing renal impairment after 12 months.

Patients treated with belatacept experienced fewer serious side effects, including lower rates of new-onset diabetes and better blood pressure and lipid levels compared to those on cyclosporine, indicating a potentially safer profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. Garnock-Jones, KP.[2016]

References

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

Belatacept in kidney transplantation. [2018]

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]

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]

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

Belatacept: from rational design to clinical application. [2017]

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]

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]

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

Belatacept: in adult kidney transplant recipients. [2016]