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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of using only belatacept, a drug that helps prevent organ rejection, in kidney transplant patients. It targets those who participated in a previous study and are now being evaluated to see if they can safely reduce other medications and rely mainly on belatacept. Participants should have steady kidney function and no antibodies against the donor kidney. Those who completed the earlier study and have stable kidney health may find this trial suitable. As an unphased trial, it offers a unique opportunity to contribute to ongoing research and potentially benefit from a more streamlined medication regimen.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that belatacept is generally well-tolerated by kidney transplant patients. In one study, serious side effects occurred in about 68% of patients receiving belatacept every four weeks and in 73% of those receiving it every eight weeks. Over five years, patients using belatacept maintained stable kidney function, indicating their kidneys continued to work well without major changes.

However, there is a risk of rejection, which affected about 24% of patients within the first year after switching to belatacept. Rejection occurs when the body's immune system attacks the transplanted kidney. Despite this risk, long-term use of belatacept reduced the risk of death by 38% to 45%, depending on treatment frequency.

Overall, while serious side effects can occur, belatacept has maintained kidney function over time and may offer long-term benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Belatacept is unique because, unlike traditional immunosuppressive treatments for kidney transplant patients, which often involve a cocktail of drugs, it offers a simplified approach. Most treatments rely on a multi-drug regimen to prevent organ rejection, but Belatacept works differently by targeting a specific pathway to inhibit T-cell activation, reducing the need for multiple medications. Researchers are excited about Belatacept because it might minimize side effects associated with long-term use of other immunosuppressants and potentially improve kidney function and patient outcomes. This precision medicine approach could personalize treatment, making it a promising option for those whose immune systems are more stable.

What evidence suggests that belatacept monotherapy could be an effective treatment for kidney transplant patients?

Research shows that belatacept works well for kidney transplant patients. In this trial, some participants will undergo an immunosuppression taper to transition to belatacept monotherapy. Studies have found that the chance of the body rejecting the new kidney with belatacept is about 8% to 12% in the first year. In another study, patients using belatacept had a 38% to 45% lower risk of death over seven years compared to those on a different treatment. Additionally, patients who switched to belatacept demonstrated better kidney function after one year. Overall, belatacept offers a strong option for long-term success in kidney transplants. ^{2 3 5 6 7}

Who Is on the Research Team?

David Wojciechowski, DO

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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, 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5724691/

Ten‐year outcomes in a randomized phase II study of kidney ...

Cumulative BPAR rates from second randomization to year 10 for belatacept 4‐weekly, belatacept 8‐weekly, and cyclosporine were 11.1%, 21.9%, and 13.9%, ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1506027

Belatacept and Long-Term Outcomes in Kidney ...

The reduction in the risk of death at 7 years was 38% with the more-intensive belatacept regimen and 45% with the less-intensive regimen as ...

3.

frontierspartnerships.org

frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14412/full

Belatacept in Kidney Transplantation: Reflecting on the Past ...

This regimen has proven to be highly effective, with biopsy-proven acute rejection (BPAR) rates of approximately 8%–12% within the first year ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468024925001597

One-Year Outcomes After Belatacept Conversion in ...

When looking at the eGFR evolution rate at the individual level, stable patients on belatacept showed significant improvement in graft function at 1 year and a ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11108246/

Long-Term Outcomes after Conversion to a Belatacept ...

After a mean follow-up time of 5.6 (2.6) years after conversion, 67 patients (28%) died in the belatacept group while 87 patients (36%) died in the CNI control ...

6.

nulojixhcp.bmscustomerconnect.com

nulojixhcp.bmscustomerconnect.com/pooled-safety.html

Selected Pooled Safety Data

Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss; consider reduction in immunosuppression, weighing risk to the ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3013525/

Five-Year Safety and Efficacy of Belatacept in Renal ...

Renal function was stable in belatacept patients over the 5-year period. Average calculated GFR was 75.8 ± 20.1 ml/min per 1.73 m2 in LTE belatacept recipients ...