Belatacept for Heart Transplant

Recruiting at 3 trial locations

Overseen By Yvonne Morrison

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Tacrolimus, Mycophenolate, Corticosteroids

Must not be taking: Immunosuppressive biologics

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 9 months

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to prevent rejection in heart transplant recipients by comparing two treatments. One treatment uses the standard drug tacrolimus, while the other gradually replaces it with belatacept (Nulojix), a medication aimed at reducing rejection risk. Researchers aim to determine if belatacept is safe and effective in preventing serious problems, such as rejection and the need for another transplant, within 18 months post-transplant. This trial may suit individuals who have recently undergone their first heart transplant and tested positive for Epstein-Barr Virus, a common virus most people encounter in childhood. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in transplant care.

Do I need to stop my current medications to join the trial?

The trial involves a gradual withdrawal of tacrolimus over 9 months for those in the belatacept group. Other medications like CellCept® or Myfortic® and corticosteroids will be continued. The protocol does not specify if you need to stop other current medications, so it's best to discuss with the study team.

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

Research shows that belatacept, a drug used to prevent the body from rejecting a new heart, is safe for heart transplant patients. Studies have found that patients can safely use it with other medications, even those with kidney problems or a higher risk of immune reactions. Belatacept is linked to better kidney function and a low rate of transplant rejection. This means it helps protect the new heart while being gentle on the kidneys, a common concern after a transplant.

While this trial aims to explore its use further, existing research provides a reassuring picture of belatacept's safety in transplant situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Belatacept for heart transplant patients because it offers a novel approach to immunosuppression. Unlike the standard treatment that relies heavily on calcineurin inhibitors like tacrolimus, Belatacept works by selectively blocking a specific signal required for T-cell activation, potentially reducing the risk of kidney damage associated with long-term use of calcineurin inhibitors. Additionally, this mechanism might lead to fewer side effects and better long-term outcomes, making it a promising alternative for maintaining immune balance and improving the quality of life for heart transplant recipients.

What evidence suggests that belatacept might be an effective treatment for heart transplant patients?

This trial will compare Belatacept with standard-of-care treatments for heart transplant patients. Research has shown that Belatacept benefits kidney transplant patients by extending their lives and maintaining kidney function. Although less information exists for heart transplant patients, early results are promising and suggest it might help maintain heart health. Studies on Belatacept in heart transplants have noted possible improvements in patient health and fewer complications compared to traditional drugs. Belatacept aims to lower the risk of organ rejection and may improve overall health by reducing the need for other drugs with harmful side effects. ^{3 4 6 7 8}

Who Is on the Research Team?

Christian P. Larsen, MD, DPhil

Principal Investigator

Emory University

Joren C Madsen, MD, DPhil

Principal Investigator

Massachusetts General Hospital

Jon A. Kobashigawa, MD

Principal Investigator

Cedars-Sinai Medical Center

Marlena Habal, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for primary heart transplant recipients. Participants must be eligible for a heart transplant and fit to undergo the procedure. Specific inclusion or exclusion criteria are not listed, but typically these would exclude individuals with certain medical conditions or those taking conflicting medications.

Inclusion Criteria

Study entry: Subject must be able to understand the purpose of the study and be willing to participate and provide written consent

Study entry: Epstein-Barr Virus (EBV) seropositive

Randomization: Negative crossmatch actual or virtual on the most recent sera

Exclusion Criteria

Study entry: Abnormal white blood cell count or neutrophil count

Randomization: Known hypersensitivity to specific medications

Randomization: Positive for certain infections or diseases

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard-of-care tacrolimus-based immunosuppression or a belatacept-based regimen with gradual tacrolimus withdrawal over 9 months post-transplant

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of chronic kidney disease stage

9 months

Assessed at Baseline, Month 1, 12, and 18

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept

Trial Overview The study compares standard tacrolimus-based immunosuppression with a belatacept-based regimen where tacrolimus is gradually withdrawn over 9 months post-transplant. Both groups will also receive mycophenolate mofetil/sodium and corticosteroids.

How Is the Trial Designed?

Group I: Belatacept + Tacrolimus withdrawal Experimental Treatment 4 Interventions

1. Maintenance Immunosuppression: NULOJIX (belatacept) 2. Maintenance Immunosuppression: CellCept (mycophenolate mofetil- MMF), or Myfortic (mycophenolate sodium) 3. Calcineurin Inhibitors (CNI) Taper: Prograf® (tacrolimus), or tacrolimus generic 4. Corticosteroid: Prednisone (no less than 5mg per day continued throughout the study period)

Group II: Standard-of-Care Active Control 3 Interventions

1. Maintenance Immunosuppression: Prograf (tacrolimus), or tacrolimus generic; 2. Maintenance Immunosuppression: CellCept (mycophenolate mofetil- MMF), or Myfortic (mycophenolate sodium); 3. Corticosteroid +/- taper: Prednisone

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?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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 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 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, approved by the FDA in 2011 for kidney transplantation, selectively blocks T cell costimulation and has shown promising results in improving both short- and long-term outcomes in renal transplants, while having a better side effect profile compared to traditional calcineurin inhibitors (CNIs).

The use of belatacept may help reduce the nephrotoxicity and metabolic side effects associated with CNIs, addressing the significant issues of chronic kidney disease and its related complications in solid organ transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept As an Alternative to Calcineurin Inhibitors in Patients with Solid Organ Transplants. Kumar, D., LeCorchick, S., Gupta, G.[2020]

In a study involving 4 liver transplant patients who were switched from belatacept to triple therapy, all experienced acute rejection and graft dysfunction after a mean of 10.3 weeks on MMF monotherapy, indicating that belatacept does not provide sufficient immunomodulatory effects to allow for safe withdrawal.

Despite initial superior kidney function (eGFR of 105.1 mL/min/1.73 m²) in belatacept patients compared to controls (58 mL/min/1.73 m²), kidney function declined significantly after switching to CNI therapy, highlighting the need for careful management of immunosuppressive therapy in liver transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept treatment for two yr after liver transplantation is not associated with operational tolerance. Schwarz, C., Rasoul-Rockenschaub, S., Soliman, T., et al.[2016]

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, 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 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]

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. 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 ...

3. 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.

4. 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.

5. 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.

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. jhltopen.org jhltopen.org/article/S2950-1334(25)00072-2/fulltext

Belatacept-based immunosuppression in heart transplant ... We aim to describe the effect of belatacept on de novo donor-specific antibodies (DSA) formation, rejection, and renal function in heart transplant recipients.