Belatacept for Heart Transplant

Recruiting at 3 trial locations

Overseen By Dylan McDonald

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marlena V. Habal

Must not be taking: Immunosuppressives, Cytolytics, DMARDs, others

Disqualifiers: Multiorgan transplant, Low eGFR, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are actively being treated with immunosuppressive therapies or certain other treatments, you may not be eligible to participate.

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

Belatacept has been shown to improve kidney function and reduce the risk of graft loss and death in kidney transplant patients, which suggests it might also be beneficial in heart transplant patients. It offers a lower cardiovascular risk profile compared to traditional drugs like cyclosporine, although it may increase the risk of certain infections. ^{1 2 3 4 5}

Is Belatacept safe for use in humans?

Belatacept has been studied primarily in kidney and liver transplant patients, showing a generally safe profile with some risks. It may increase the risk of certain infections and conditions like posttransplant lymphoproliferative disorder, especially in patients with certain viral infections, but it is associated with a lower cardiovascular risk compared to some other treatments. ^{3 4 6 7 8}

How is the drug Belatacept unique for heart transplant patients?

Belatacept is unique because it offers an alternative to calcineurin inhibitors, which can harm kidney function, and it has been shown to improve long-term outcomes in kidney transplant patients. Its use in heart transplant patients is emerging, potentially offering similar benefits by reducing kidney damage and improving overall survival. ^{1 3 9 10 11}

What is the purpose of this trial?

This trial is testing if Belatacept is safe for adult heart transplant patients. The medication helps prevent organ rejection by calming the immune system. It aims to improve long-term outcomes for these patients. Belatacept has shown promise in preserving kidney function in previous studies.

Research Team

Marlena Habal, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults aged 18-75 awaiting a primary heart transplant, who are EBV seropositive and can take oral meds. They must adhere to belatacept infusion schedule, have up-to-date vaccinations, and females of childbearing age need a negative pregnancy test. Excludes those with prior transplants, certain infections like HIV/HBV/HCV/TB, recent live vaccines, cancer in the last 5 years, high PRA levels or severe allergies to monoclonal antibodies.

Inclusion Criteria

You are waiting to receive a new heart.

I have not undergone desensitization therapy before a transplant.

I am in a trial for a device or drug that ends with my transplantation.

Exclusion Criteria

If you have any medical issues that aren't mentioned in the criteria above, and they might interfere with your ability to participate in the study or affect the accuracy of the results, you may not be eligible.

I am not currently in a trial that involves treatment at the time of my transplant.

I do not have any active infections, except for possible driveline infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Belatacept along with mycophenolate mofetil, corticosteroids, and a tacrolimus tapering regimen

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Belatacept
• Corticosteroid
• Mycophenolate Mofetil
• Tacrolimus

Trial Overview The trial is testing if Belatacept is safe for adult heart transplant recipients as an anti-rejection medication. It's being used investigatively alongside standard post-transplant drugs such as corticosteroids, tacrolimus and mycophenolate mofetil.

Participant Groups

Group I: Belatacept Experimental Treatment 4 Interventions

Participants will receive Belatacept along with an upfront tacrolimus taper Participants will also receive mycophenolate mofetil and corticosteroids are part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice.

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?

Marlena V. Habal

Lead Sponsor

Trials

1

Recruited

10+

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Bristol-Myers Squibb

Industry 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

Findings from Research

Belatacept, approved by the FDA in 2011, provides a safer alternative to calcineurin inhibitors for renal transplant patients, showing improved renal function and a 43% reduction in the risk of graft loss and death over seven years in the BENEFIT trial involving multiple centers.

While primarily used in renal transplantation, emerging reports suggest successful long-term use of belatacept in other transplant settings, including kidney-after-heart transplants, indicating its potential versatility beyond just kidney transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De Novo Belatacept in a Kidney-After-Heart Transplant Recipient. Schenk, AD., Anderson, DJ., Cole, RT., et al.[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]

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 has shown comparable efficacy to cyclosporine in preventing organ rejection, but a more intensive treatment regimen increased the risk of rejection and posttransplant lymphoproliferative disorder, especially in patients with Epstein-Barr virus.

Tasocitinib demonstrated good prophylaxis against rejection in a phase II trial, but it also raised safety concerns such as increased infection risk and potential blood cell reductions, while both drugs were associated with lower cardiovascular risks and improved kidney function compared to cyclosporine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of emerging immunosuppressive strategies to improve the posttransplant cardiovascular risk profile. Djamali, A., Pietrangeli, CE., Gordon, RD., et al.[2021]

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]

In a study of 34 patients at high cardiovascular risk, Belatacept treatment led to a significant increase in estimated glomerular filtration rate (eGFR) compared to a matched control group on calcineurin inhibitors, indicating better kidney function with Belatacept.

Belatacept was found to be safe, with no significant increase in risks for renal allograft rejection, severe infections, or other serious complications, making it a promising immunosuppressive option for renal transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Belatacept Treatment in Renal Allograft Recipients at High Cardiovascular Risk-A Single Center Experience. Neuwirt, H., Leitner-Lechner, I., Kerschbaum, J., et al.[2020]

In a phase II study involving 260 de novo adult liver transplant recipients, belatacept treatment groups experienced a higher rate of acute rejection, graft loss, and death by month 6 compared to tacrolimus groups, indicating potential safety concerns with belatacept.

Despite the higher rates of complications, belatacept-treated patients had better kidney function (measured by GFR) at 1 year, suggesting a possible benefit in renal preservation, although the study was ultimately terminated due to increased adverse outcomes in belatacept groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study. Klintmalm, GB., Feng, S., Lake, JR., et al.[2023]

In a study of 27 kidney transplant recipients, the combination of belatacept (Bela) with mycophenolate (MPA) led to a high rate of acute rejection, resulting in the early closure of this treatment arm, with 4 out of 9 patients experiencing rejection.

Conversely, the regimen of belatacept with low-dose tacrolimus (Tac) showed a trend towards improved kidney function, with an increase in estimated glomerular filtration rate (eGFR), suggesting that low-dose Tac may be necessary to prevent rejection when using belatacept in steroid-free regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early calcineurin-inhibitor to belatacept conversion in steroid-free kidney transplant recipients. Tawhari, I., Hallak, P., Bin, S., 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 proof-of-concept study involving 12 kidney transplant recipients, a regimen combining belatacept, mycophenolic acid, steroids, and rabbit anti-thymocyte globulin significantly reduced acute rejection rates, with only 2 out of 12 patients experiencing rejection.

The study demonstrated that this treatment approach was safe, as no patients developed serious complications like post-transplant lymphoproliferative disorder, and all patients maintained their grafts without any deaths during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study. Cicora, F., Mos, F., Petroni, J., et al.[2015]

In a 3-year study involving extended criteria donor kidney transplant recipients, belatacept showed similar patient and graft survival rates compared to cyclosporine, with 86% to 89% survival for belatacept versus 85% for cyclosporine at 12 months.

Belatacept treatment resulted in better renal function, with a mean glomerular filtration rate 4-7 mL/min higher than cyclosporine, although it was associated with a higher incidence of posttransplant lymphoproliferative disorder (PTLD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Durrbach, A., Pestana, JM., Pearson, T., et al.[2023]

References

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

De Novo Belatacept in a Kidney-After-Heart Transplant Recipient. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Belatacept in kidney transplantation. [2018]

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

Potential of emerging immunosuppressive strategies to improve the posttransplant cardiovascular risk profile. [2021]

5. 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]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Belatacept Treatment in Renal Allograft Recipients at High Cardiovascular Risk-A Single Center Experience. [2020]

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

Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Early calcineurin-inhibitor to belatacept conversion in steroid-free kidney transplant recipients. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Belatacept utilization recommendations: an expert position. [2015]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study. [2015]

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

A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). [2023]