Belatacept-Only Immunosuppression for Kidney Transplant

Overseen By David Wojciechowski, DO

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Pregnancy, Hepatic impairment, Proteinuria, others

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

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

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Belatacept is used as an alternative to other drugs for maintaining kidney transplants, and it has a favorable cardiovascular profile, making it an attractive option for patients with systemic lupus erythematosus who receive kidney transplants. ^{1 2 3 4 5}

Is Belatacept safe for use in kidney transplant patients?

Belatacept is generally considered safe for kidney transplant patients, but it may lead to more episodes of cellular rejection and a higher risk of post-transplant lymphoproliferative disorder (a type of cancer) in certain patients, especially those who are EBV seronegative (not previously infected with Epstein-Barr virus). ^{6 7 8 9 10}

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

Belatacept is unique because it is a biological drug that blocks a specific pathway (CD28 on T cells) to prevent organ rejection, unlike traditional treatments that often rely on calcineurin inhibitors. It offers benefits like better kidney function and a lower risk of heart problems, but it may increase the risk of certain infections, especially in patients who haven't been exposed to the Epstein-Barr virus. ^{6 7 8 10 11}

What is the purpose of this trial?

The purpose of the study is to provide immunosuppression weaning and/or monitoring for an additional 12-months to evaluate the safety and efficacy of belatacept monotherapy in patients previously enrolled in the clinical trial: "Use of donor derived-cell free DNA (AlloSure) and gene expression profiling (AlloMap Kidney) to facilitate Belatacept monotherapy in kidney transplant patients."

Research Team

David Wojciechowski, DO

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for kidney transplant recipients who completed the parent study STU-2020-1339, can consent to participate, don't have donor-specific antibodies, and have stable kidney function (eGFR>40mL/min). Pregnant or lactating women, those planning pregnancy during the trial, individuals with significant protein in urine or liver issues are excluded.

Inclusion Criteria

Completion of the parent study (STU-2020-1339)

Able to provide informed consent

Absence of donor specific antibodies

Exclusion Criteria

I am not pregnant, breastfeeding, or planning to become pregnant during the trial.

Proteinuria > 0.5 g/g creatinine on spot urine sample within 3 months of enrollment

I have severe liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immunosuppression Taper

Eligible patients undergo sequential withdrawal of immunosuppression medications over a 12-month period to transition to Belatacept monotherapy

12 months

Multi-Drug Regimen

Eligible patients who are not deemed immune quiescent continue on a multi-drug regimen

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Belatacept

Trial Overview The study tests if it's safe and effective to reduce immunosuppression drugs to just belatacept over an additional 12 months. It uses DNA testing (Allosure) and gene expression profiling (TruGraf) for monitoring patients previously on belatacept monotherapy.

Participant Groups

Group I: Multi-Drug Regimen Experimental Treatment 1 Intervention

Eligible patients who are not deemed immune quiescent will continue on a multi-drug regimen.

Group II: Immunosuppression Taper Experimental Treatment 2 Interventions

Eligible patients who are deemed immune quiescent will undergo sequential withdrawal of immunosuppression medications over a 12-month period from a multi-drug regimen to a Belatacept monotherapy using precision medicine.

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+

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplant patients with systemic lupus erythematosus. [2022]

2. Czech Republic pubmed.ncbi.nlm.nih.gov

What is new in the treatment of Systemic Lupus Erythematosus? [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

The use of belimumab in three cases of refractory lupus nephritis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Immunotherapy for autoimmune and inflammatory renal diseases. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

[Biologicals and small molecules for systemic lupus erythematosus]. [2021]

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

Belatacept in kidney transplantation. [2018]

7. 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]

8. 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]

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

Belatacept: a new biologic and its role in kidney transplantation. [2015]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. 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]