Belatacept in Heart Transplantation

NCT06478017 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT RTB-013
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase 2, prospective, multi-center, open-label clinical trial. Sixty-six (66) primary heart transplant recipients will be randomized (1:2) to receive either standard-of-care, tacrolimus-based immunosuppression, or a belatacept-based regimen with gradual tacrolimus withdrawal over 9-months post-transplant. Both study arms will receive CellCept® (mycophenolate mofetil- MMF) or Myfortic® (mycophenolate sodium). Corticosteroids will be continued throughout the study in the belatacept arm. The primary objective is to evaluate whether NULOJIX® (belatacept), when implemented with gradual tacrolimus withdrawal over 9 months, is safe with respect to preventing the composite endpoint of acute cellular rejection (ACR) \>= International Society of Heart and Lung Transplantation (ISHLT) 2R, hemodynamic compromise rejection in the absence of a biopsy or histological rejection, re-transplantation, and death at 18 months post-transplant.

Conditions

Heart Transplant

Keywords

Heart transplant; Transplantation; Standard of care; Belatacept; Tacrolimus

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who experience acute cellular rejection (ACR) >ISHLT 2R (local or core read), hemodynamic compromise (HDC) rejection in the absence of a biopsy or histological rejection, re-transplantation, or death as a composite endpoint.

  From randomization to 18 months post-transplantation

Secondary Outcomes (23)

• Slope of estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation

  From baseline to 18 months post-transplantation, assessed at Baseline, Randomization, Month 1, 6 and 18

• Proportion of subjects with eGFR <60mL/min/1.73m^2 measured by CKD-EPI

  From randomization to 18 months post-transplantation

• Proportion of subjects with eGFR<45mL/min/1.73m^2 measured by CKD-EPI

  From randomization to 18 months post-transplantation

• Mean change in albumin/creatinine ratio in urine

  From baseline to 18 months post-transplantation

• Change in Chronic Kidney Disease (CKD) stage measured using the mean difference on a continuous measurement scale

  From Baseline to 18 months post-transplantation, assessed at Baseline, Month 1, 12 and 18

Study Arms (2)

Belatacept + Tacrolimus withdrawal

EXPERIMENTAL

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)

Drug: Belatacept; Drug: Tacrolimus; Drug: Mycophenolate Mofetil/Sodium; Drug: Prednisone

Standard-of-Care

ACTIVE COMPARATOR

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

Drug: Tacrolimus; Drug: Mycophenolate Mofetil/Sodium; Drug: Prednisone

Interventions

Belatacept DRUG

Patients will receive 10mg/kg on Day 3 post-transplant (72 hours +/- 12 hours post-transplant) Day 7 post-transplant (+/- 6 hours) Day 16 (End of Week 2 after 1st dose of belatacept) post-transplant (+/- 2 days) Day 30 (End of Week 4 after 1st dose of belatacept) post-transplant (+/- 3 days) Day 58 (Week 8) post-transplant (+/- 3 days) Day 86 (Week 12) post-transplant (+/- 3 days) Patients will receive 5mg/kg Every 28 days (+/- 3 days) thereafter

Also known as: NULOJIX

Belatacept + Tacrolimus withdrawal

Tacrolimus DRUG

Prograf (tacrolimus) or tacrolimus generic

Also known as: Prograf

Belatacept + Tacrolimus withdrawal; Standard-of-Care

Mycophenolate Mofetil/Sodium DRUG

CellCept (mycophenolate mofetil- MMF), or Myfortic (mycophenolate sodium)

Also known as: CellCept, Myfortic

Belatacept + Tacrolimus withdrawal; Standard-of-Care

Prednisone DRUG

Prednisone

Belatacept + Tacrolimus withdrawal; Standard-of-Care

Eligibility Criteria

• Age: 18 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study entry
• Subject must be able to understand the purpose of the study and be willing to participate and provide written consent
• Recipient of a primary heart transplant (heart transplant only)
• Epstein-Barr Virus (EBV) seropositive (VCA IgG, EBNA IgG). If EBNA is not available, enrollment may proceed but the result must be available prior to randomization.
• Agreement to use contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study
• In the absence of a contraindication, vaccinations must be up to date per the Division of Allergy, Immunology, and Transplantation (DAIT) Vaccination Guidance for Patients in Transplant Trials (niaidtransplantstudies.org)
• Mechanical support or investigational drug trials where the intervention ends at the time of transplantation are permitted.
• Randomization
• Recipient of a primary heart transplant
• No desensitization therapy prior to transplant
• Negative crossmatch actual or virtual, on the most recent sera as determined by the participating study center
• Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) prior to randomization
• Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug
• Pre-transplant eGFR (CKD-epi) \>30ml/min/1.73m\^2. If eGFR \<30ml/min/1.73m\^2 at the time of randomization, participation is permitted if the study physician determines that renal recovery is expected. Participants who are on dialysis at randomization or are expected to require dialysis at or after randomization will not be permitted to participate.

You may not qualify if:

• Study entry
• Candidate for multiple solid organ or tissue transplants
• Prior history of any organ, tissue, or cellular transplant
• Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period
• History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies
• Known hypersensitivity to NULOIX (belatacept) or ORENCIA (Abatacept)
• Previous treatment with NULOIX (belatacept) or ORENCIA (Abatacept)
• Epstein Barr Virus (EBV) seronegative or indeterminant
• Human Immunodeficiency Virus (HIV) positive
• Hepatitis B surface antigen positive
• Hepatitis B core antibody positive
• Hepatitis C virus antibody (HCV Ab+) and hepatitis C virus (HCV) Polymerase Chain Reaction (PCR) positive patients
• Patients with active Tuberculosis (TB) in the past 2 years, whether or not it was adequately treated; patients with documented treatment of active TB greater than 2 years ago will be allowed to participate if there is documentation of adequate treatment according to locally accepted clinical practice
• Subjects must be tested for latent TB infection (LTBI) within a year prior to transplant. Testing should be conducted using either a PPD or Interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Patients with a positive test for latent TB infection (LTBI) must have completed appropriate therapy for LTBI (https://www.cdc.gov/tb/topic/treatment/ltbi.htm). A subject is considered eligible only if they have a negative test for LTBI within one year prior to transplant OR if they have completed appropriate LTBI therapy within one year prior to transplant
• Positive serology for T. cruzi or known/suspected history of Chagas disease

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

Cedars Sinai Heart Institute/ Cedars Sinai Medical (Site # 71146)

Los Angeles, California, 90048, United States

RECRUITING

Tampa General Hospital (Site # 71150)

Tampa, Florida, 33606, United States

RECRUITING

NYU Langone Health (Site # 71177)

New York, New York, 10016, United States

RECRUITING

University of Utah Medical Center (Site # 71126)

Salt Lake City, Utah, 84132, United States

RECRUITING

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Interventions

Abatacept; Tacrolimus; Mycophenolic Acid; Sodium; Prednisone

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Joren C Madsen, MD, DPhil

  Massachusetts General Hospital

  STUDY CHAIR

• Jon A. Kobashigawa, MD

  Cedars-Sinai Medical Center

  STUDY CHAIR

• Marlena Habal, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Christian P. Larsen, MD, DPhil

  Emory University

  STUDY CHAIR

Central Study Contacts

Yvonne Morrison

CONTACT

301-706-9137; ymorrison@niaid.nih.gov

Jaclyn Evans

CONTACT

240-669-5470; Jaclyn.evans@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 27, 2024
• Study Start: January 29, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)