Belatacept in De Novo Heart Transplantation

Belatacept in De Novo Heart Transplantation - Pilot Study

The purpose of this study is to determine if Belatacept is safe to give to adult heart transplant recipients. Belatacept (NULOJIX) is an anti-rejection medication that is available through a prescription from a doctor. In this research study, belatacept is being used in an investigational manner (not for the purpose that it is approved for).

Study Overview

• Status: Recruiting
• Conditions: Heart Transplantation
• Intervention / Treatment: Drug: Belatacept; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Corticosteroid

Detailed Description

Long-term outcomes after heart transplant remain suboptimal with renal failure and cardiac allograft vasculopathy contributing to morbidity and mortality. Belatacept is Food and Drug Administration (FDA) approved for use in kidney transplant recipients on the basis of two randomized controlled trials, which demonstrated important renal sparing benefits, a reduction in de novo donor-specific antibodies (DSA), and improved long-term outcomes. In this study, ten (10) primary heart transplant recipients will receive belatacept in addition to mycophenolate mofetil, corticosteroids, and a tacrolimus tapering regimen.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea Kim; Phone Number: 646-457-0987; Email: Andrea.Kim@nyulangone.org
• Study Contact Backup: Name: Dylan McDonald; Email: Dylan.Mcdonald@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Andrea Kim; Email: Andrea.Kim@nyulangone.org
      • Principal Investigator: Marlena Habal, MD
    • New York, New York, United States, 10032
      • Active, not recruiting
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or non-pregnant female, age ≥18 to ≤75 years
2. Awaiting a primary heart transplant (listed for heart transplant only)
3. Epstein-Barr virus (EBV) IgG seropositive
4. Able to take oral medication and willing to adhere to the belatacept infusion regimen
5. No desensitization therapy prior to transplant
6. Vaccinations should be up to date for hepatitis B, influenza pneumococcal, haemophilus, varicella zoster virus (VZV), measles, mumps and rubella (MMR), and Human Papilloma Virus (HPV) (for participants < 45 years of age) when available
7. Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) prior to randomization
8. Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted
9. Negative virtual crossmatch

Exclusion Criteria:

1. Candidates awaiting multiorgan transplant
2. Estimated glomerular filtration rate (eGFR) < 45 ml/min/m2
3. Candidates with prior organ transplant
4. Candidates actively being treated with immunosuppressive therapies
5. Candidates who have a history of treatment with cytolytic therapy (e.g. anti-thymocyte globulin)
6. Candidates who are intended to be treated with cytolytic therapy in the post-transplant period as induction therapy
7. EBV (IgG) seronegative
8. Active or prior infection with human immunodeficiency virus (HIV), Hepatitis C (HCV), Hepatitis B (HBV)
9. Untreated latent tuberculosis (TB)
10. All potential candidates will be screened prior to enrolment for a history of tuberculosis (chest radiograph and tuberculosis-Interferon Gamma Release Assay (TB-IGRA) or tuberculin skin tests (TST)). Potential candidates with latent TB must be treated prior to study enrolment
11. Prior history of active tuberculosis
12. Prior history of central nervous system infection
13. Known active current viral, fungal, mycobacterial, or other infections excluding driveline infections - potential participants from endemic areas will additionally be screened for histoplasmosis, blastomycosis, coccidioidomycosis, and strongyloidiasis
14. Vaccination with a live vaccine within the past 30 days
15. Malignancy within the last 5 years
16. Any previous treatment with alkylating agents or total lymphoid irradiation
17. Sensitized heart transplant candidates with panel-reactive antibodies (PRA) >50% or those receiving desensitization treatment
18. Prior treatment with belatacept or abatacept
19. History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies
20. Treatment with a disease modifying anti-rheumatic drug (DMARD) or other biologic agent (monoclonal antibody) within the past year
21. Treatment with another investigational drug or other intervention at the time of transplant (excluding device or intervention mechanical support or investigational drug trials where the intervention ends at the time of transplant)
22. Potential candidates for whom a calcineurin inhibitor other than tacrolimus (Prograf®) is anticipated after transplant. If during the course of the study, a participant is transitioned to another calcineurin inhibitor due to side effects or inability to achieve stable therapeutic trough levels, they may continue in the study at the discretion of the investigator
23. Any potential participant who remains on mechanical circulatory support for > 72 hours post-transplant will be excluded from the study
24. The need for ongoing high dose vasopressor support > 72 hours post-transplant
25. The need or anticipated need for post-transplant dialysis
26. Platelet count <75,000/mm (within 24 hours prior to transplant)
27. Absolute neutrophil count (ANC) of less than 2000/mm3 within 24 hours prior to transplant
28. Any past or current medical problems or findings on history, physical examination, or laboratory testing, not listed above, that in the opinion of the investigator, may pose additional risk to participation, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Belatacept; 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.

Drug: Belatacept; Belatacept will be given in the following way - 10mg/kg IV day 1, 5, end of weeks 2, 4, 8, 12 then 5mg/kg every 4 weeks.; Other Names: Nulojix; Drug: Tacrolimus; Non-experimental: Tacrolimus will be given in the following way - trough level at month 1, 10-12ng/mL; month 2-3, 6-10ng/mL; month 4-6, 4-6ng/mL; months 7-9 taper off.; Other Names: Tacrolimus taper; Drug: Mycophenolate Mofetil; Non-experimental: MMF is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at 500-1500mg twice a day (BID) (dosed to tolerance and effect).; Other Names: MMF; Drug: Corticosteroid; Non-experimental: CS is part of standard of care after heart transplant and will follow dosing recommendations as per standard clinical practice at a dose no less than 5mg/d.; Other Names: CS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Major Graft-Related Adverse Events	Adverse events that will be counted in the total number include: Episodes of acute cellular rejection ≥ 2R/3A, antibody mediated rejection (AMR) ≥ International Society of Heart and Lung Transplantation (ISHLT) AMR 1, hemodynamically compromised rejection, development of cardiac allograft vasculopathy, graft failure occurring ≥ 14 days post-transplant, the need for re-transplant, serious infection requiring inpatient intravenous therapies, post-transplant lymphoproliferative disorder (PTLD), or death.	Up to 18 months after transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Estimated Glomerular Filtration Rate (eGFR)	Baseline and 18 months
Percentage of Individuals with Development of De Novo Donor Specific Antibodies (DSA)	18 months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Marlena V. Habal, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Heart Transplant; Nulojix
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Immunoconjugates; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Caproates; Abatacept; Mycophenolic Acid; Tacrolimus; Adrenal Cortex Hormones
• Other Study ID Numbers: 22-01135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No