Belatacept Regimen for Kidney Transplant Recipients

Recruiting at 57 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: < 18

Sex: Any

Trial Phase: Phase 3

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for young kidney transplant recipients. Researchers aim to determine if switching to a belatacept-based treatment is more effective than continuing with current medications. Belatacept (also known as Nulojix) is being tested alongside other treatments like corticosteroids and cyclosporine A. The trial seeks participants who have been stable on their current medications, have good kidney function, received their transplant more than six months ago, and have been vaccinated against COVID-19. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that belatacept is generally safe for kidney transplant patients. In one study, most patients remained healthy, and their kidneys functioned well even after five years. Another study found that patients taking belatacept had a lower risk of death over seven years compared to those on other treatments. Patients who switched to belatacept also demonstrated better kidney function after one year.

However, some risks exist. Belatacept can cause polyoma virus-associated nephropathy, which may damage the kidneys. Doctors might need to adjust the dose to balance benefits and risks. Overall, belatacept appears safe for many patients, but discussing these risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for kidney transplant recipients?

Researchers are excited about belatacept for kidney transplant recipients because it offers a distinct approach to preventing organ rejection. Unlike traditional treatments like cyclosporine A and tacrolimus, which are calcineurin inhibitors (CNIs) that suppress the immune system broadly, belatacept selectively targets specific immune pathways. This targeted action could potentially reduce the side effects associated with CNIs, such as kidney toxicity and cardiovascular issues. Plus, belatacept is administered less frequently, improving the convenience for patients.

What evidence suggests that this trial's treatments could be effective for kidney transplant recipients?

Research has shown that using belatacept in kidney transplant treatments can lead to better outcomes. In this trial, one group of participants will switch from a calcineurin inhibitor (CNI)-based regimen to a belatacept-based regimen. Studies have found that patients on belatacept had a lower chance of dying or losing their transplanted kidney compared to those continuing on traditional CNI treatments. Specifically, after 7 years, the risk of death was reduced by 38% to 45% for those using belatacept. Additionally, patients who switched to belatacept often experienced improved kidney function over time. These findings suggest that belatacept could be a promising option for kidney transplant patients. ^{3 4 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept
• Corticosteroids
• Cyclosporine A
• Enteric Coated Mycophenolate Sodium
• Mycophenolate Mofetil
• Tacrolimus

Trial Overview

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.

How Is the Trial Designed?

Group I: Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Experimental Treatment 6 Interventions

Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI)

Group II: Arm 2: Continue calcineurin inhibitor-based regimen Active Control 5 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

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

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, an immunosuppressant approved for preventing kidney graft rejection, showed similar graft survival rates compared to ciclosporin after 3 years in two large trials with over 1,200 patients, but only a high dose of belatacept improved renal function, which is not the authorized dose.

However, belatacept was associated with a higher risk of certain lymphomas and severe infections, such as progressive multifocal leukoencephalopathy and tuberculosis, making ciclosporin a more established and safer choice for long-term immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept. [2019]

The extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) shows similar efficacy to the immediate-release version (Prograf®) in kidney transplant recipients, with no significant differences in patient/graft survival, acute rejection rates, or renal function across studies involving over 2,500 patients.

Advagraf® significantly improves medication adherence compared to Prograf®, which is crucial for long-term transplant success, and it has also been associated with favorable outcomes when combined with mTOR inhibitors, potentially reducing the risk of late-onset cytomegalovirus infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. Noble, J., Jouve, T., Rostaing, L., et al.[2021]

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]

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 a newly approved immunosuppressive therapy for kidney transplant recipients that has been shown to improve long-term graft function and is effective in preventing kidney allograft rejection, based on data from Phase II and III clinical trials.

Unlike traditional therapies, belatacept may reduce the risk of chronic side effects associated with calcineurin inhibitors and steroids, making it a promising option for long-term immunosuppression, although it is contraindicated in patients with unknown Epstein-Barr virus serostatus due to increased risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept utilization recommendations: an expert position. Grinyó, JM., Budde, K., Citterio, F., et al.[2015]

In a 6-month trial involving 237 stable renal transplant recipients, converting from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) was found to be safe, with only 10% of patients requiring dose reductions due to adverse events.

The incidence of adverse events was 59.9%, with gastrointestinal issues being the most common at 22%, but the overall need for dose adjustments was low, indicating that EC-MPS is a tolerable alternative for patients previously on MMF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable renal transplant recipients. Massari, P., Duro-Garcia, V., Girón, F., et al.[2016]

In a study of 65 Korean patients undergoing de novo renal transplantation, enteric-coated mycophenolate sodium (Myfortic) demonstrated a low incidence of biopsy-confirmed acute rejection at 10.8% within 6 months, indicating its efficacy in preventing rejection.

The safety profile showed that while 38.8% of patients experienced gastrointestinal discomfort, only 4.5% had reactions directly linked to the drug, and the overall patient and graft survival rates were high at 98.1% and 97.0%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ju, MK., Park, SH., Kim, SJ., et al.[2022]

Belatacept shows improved renal function and lower rates of new onset diabetes compared to traditional calcineurin inhibitors (CNI) in kidney transplant recipients, based on a meta-analysis of six randomized controlled trials.

There were no significant differences in acute rejection rates between belatacept and CNIs, suggesting that belatacept may reduce CNI-related toxicity without compromising transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does belatacept improve outcomes for kidney transplant recipients? A systematic review. Talawila, N., Pengel, LH.[2018]

In a study of 638 kidney transplant recipients over 4 years, both tacrolimus formulations (Astagraf XL and Prograf) demonstrated similar patient and graft survival rates, with 93.2% and 91.2% survival respectively, compared to 91.7% for cyclosporine (CsA).

Patients on tacrolimus had a higher incidence of new-onset diabetes after transplantation (41.1% for Astagraf XL and 33.6% for Prograf) compared to 21.3% for CsA, but showed comparable renal function between the two tacrolimus formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Silva, HT., Yang, HC., Meier-Kriesche, HU., et al.[2021]

In a 24-month study of 101 kidney transplant recipients, the enteric-coated formulation of mycophenolate sodium (EC-MPS) showed a significantly lower incidence of serious infections compared to mycophenolate mofetil (MMF), with rates of 40% for EC-MPS and 49% for MMF.

The therapeutic effects of EC-MPS were found to be similar to those of MMF, as indicated by comparable serum creatinine levels and rates of biopsy-proven acute rejection, suggesting that EC-MPS is a safe and effective alternative in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Feng, JJ., Zhang, LW., Zhao, P., et al.[2016]

Converting from tacrolimus to belatacept in kidney transplant patients with stable low eGFR (< 40 mL/min) resulted in a significant improvement in eGFR, with an average increase of 11.0 mL/min compared to 4.8 mL/min in the control group over 4 months.

However, while the belatacept group showed a modest increase in kidney function, there was a higher incidence of acute rejection (16.7%) compared to the control group, indicating potential safety concerns with this conversion strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Conversion to Belatacept in Kidney Transplant Recipients With Low Glomerular Filtration Rate. Abdelwahab Elhamahmi, D., Heilman, RL., Smith, B., et al.[2022]

In a study involving 19 renal transplant recipients, the belatacept-based immunosuppressive regimen showed a higher frequency of acute cellular rejection episodes compared to the tacrolimus regimen, with 10 episodes in the belatacept groups versus only 1 in the tacrolimus group.

Despite similar estimated kidney function (GFR) at week 52 between the groups, the study was halted early due to a high rate of serious adverse events, highlighting the need for careful consideration of risks in immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. Newell, KA., Mehta, AK., Larsen, CP., et al.[2023]

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 ...

Death or graft loss status at 10 years posttransplant was assessed in 37.8% (28 of 74) of belatacept MI‐treated patients, 25.4% (18 of 71) of belatacept LI‐ ...

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.

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 ...

4.

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 ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S1600613522087159

Every 2-month belatacept maintenance therapy in kidney ...

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous ...

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 ...

At the time of data cutoff, 76% of LTE belatacept and 62% of LTE CsA recipients remained in the study; all were ≥5 years after transplantation.

8.

journals.lww.com

journals.lww.com/transplantationdirect/fulltext/2024/06000/long_term_safety_in_epstein_barr.22.aspx

Long-term Safety in Epstein–Barr Virus–Seropositive...

In both trials, belatacept treatment of kidney-only transplant recipients was associated with similar patient and graft survival, an improved cardiovascular and ...