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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Belatacept, a medication typically used to prevent organ rejection, is safe for individuals who have recently undergone a heart transplant. Participants will also receive standard medications such as corticosteroids (including Montelukast Sodium) and tacrolimus. The trial seeks individuals listed for a heart transplant who are Epstein-Barr virus positive. It excludes those with previous organ transplants or serious infections like tuberculosis. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that belatacept can be safely used as an additional treatment for heart transplant recipients. Studies have found that it improves kidney function and maintains the health of the new heart. It also appears to have a low risk of rejection, reducing the likelihood of the body attacking the new heart.

However, reports have indicated serious side effects. Out of 2,795 cases, 424 were fatal, resulting in serious outcomes in about 15% of cases. Despite this, many patients find it beneficial, particularly those with kidney issues or high immune risks. Discussing the benefits and potential risks with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Belatacept is unique because it targets a different pathway in the immune system compared to standard immunosuppressants like tacrolimus. Most treatments for heart transplant patients work by broadly suppressing the immune system, but Belatacept specifically blocks a signal needed for T-cell activation, potentially reducing long-term side effects associated with traditional therapies. Researchers are excited about Belatacept because it offers a more targeted approach, which may lead to better preservation of kidney function and fewer cardiovascular risks, making it a promising option for heart transplant recipients.

What evidence suggests that Belatacept might be an effective treatment for heart transplant recipients?

Research has shown that belatacept improves survival rates and maintains kidney function in kidney transplant patients. In this trial, participants will receive belatacept to explore its potential benefits for heart transplant patients. Although similar information for heart transplant patients is still being collected, belatacept appears promising as it may reduce the risk of organ rejection. Other studies suggest that belatacept might also help manage the complex needs of heart transplant patients. These potential benefits are under further investigation to determine their applicability to heart transplants. ^{3 6 7 8 9}

Who Is on the Research Team?

Marlena Habal, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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]

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]

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]

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]

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]

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 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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06478017?term=belatacept&rank=4

NCT06478017 | Belatacept in Heart Transplantation The primary objective is to evaluate whether NULOJIX ® ( belatacept ), when implemented with gradual tacrolimus withdrawal over 9 months, is safe with respect ...

2. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/RTB-013

Belatacept With Delayed Tacrolimus Withdrawal Versus ... This study focuses on people who are on the waitlist to receive a heart transplant. Organ transplant recipients must take medications to suppress.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053249825019588

Efficacy and safety of belatacept in heart transplant recipients Belatacept (BTC) has demonstrated mortality and graft survival benefits while preserving renal function in kidney transplant recipients, but data regarding HT ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04477629

NCT04477629 | Belatacept in De Novo Heart Transplantation Long-term outcomes after heart transplant remain suboptimal with renal failure and cardiac allograft vasculopathy contributing to morbidity and mortality.

5. amjtransplant.org amjtransplant.org/article/S1600-6135(22)22208-4/fulltext

A calcineurin inhibitor-sparing regimen in heart transplant ... Several patients were multiorgan transplant recipients. Study outcomes were GFR, safety, and changes in immunosuppressive therapy.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40446881/

Efficacy and safety of belatacept in heart transplant recipients BTC may safely be used as an adjunct immunosuppressive agent in HT recipients with renal dysfunction or elevated immunological risk.

7. jhltonline.org jhltonline.org/article/S1053-2498(22)01418-8/fulltext

The Efficacy and Safety of Belatacept in Heart Transplant ... BTC therapy resulted in improved kidney function and was associated with a low rejection rate and preserved graft function.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12341210/

Safety profile of belatacept in a real-life setting We retrieved 2795 reports involving belatacept, including 424 (15.2%) fatal cases. The disproportionality analysis highlighted 51 potential ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2950133425000722

Belatacept-based immunosuppression in heart transplant ... Recipients treated with belatacept-based regimen exhibited a trend of reduced de novo DSA development compared to standard tacrolimus-based regimen controls.