Belatacept in Heart Transplantation
NCT Number: NCT06478017
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Heart Transplant
Interventions: DRUG: Belatacept|DRUG: Tacrolimus|DRUG: Mycophenolate Mofetil/Sodium|DRUG: Prednisone
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 66
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-03
Completion Date: 2028-01-31
Locations: Cedars Sinai Heart Institute/ Cedars Sinai Medical (Site # 71146), Los Angeles, California, 90048, United States|Tampa General Hospital (Site # 71150), Tampa, Florida, 33606, United States|NYU Langone Health (Site # 71177), New York, New York, 10016, United States|University of Utah Medical Center (Site # 71126), Salt Lake City, Utah, 84132, United States

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.

Primary Outcome Measures: 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 Outcome Measures: 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, Month 1, 6 and 18|Proportion of subjects with eGFR <60mL/min/1.73m2 measured by CKD-EPI, From randomization to 18 months post-transplantation|Proportion of subjects with eGFR<45mL/min/1.73m2 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, Chronic Kidney Disease scale:

Stage 1: Glomerular Filtration Rate (GFR) \>90mL/min Stage 2: GFR = 60-89mL/min Stage 3A: GFR=45-59mL/min Stage 3B: GFR=30-44mL/min Stage 4: GFR=15-29mL/min Stage 5: GFR\<15mL/min, From Baseline to 18 months post-transplantation, assessed at Baseline, Month 1, 12 and 18|Proportion of subjects with CKD stage 4 or 5, From randomization to 18 months, assessed at Month 12 and 18|Mean difference in eGFR between the two arms, 12 months and 18 months|Proportion of subjects who are free from any detection of de novo donor-specific antibodies (dnDSA), From randomization to 18 months post-transplantation|Number of de novo donor specific antibodies per patient, From randomization to 18 months post-transplantation|Proportion of subjects who are free from ACR greater than or equal to 2R, From randomization to 18 months post-transplantation|Proportion of subjects who are free from ACR 3R, From randomization to 18 months post-transplantation|Proportion of subjects who are free from any treated rejection, From randomization to 18 months post-transplantation|Proportion of subjects who are free from antibody mediated rejection (AMR) (AMR > ISHLT AMR 1), From randomization to 18 months post-transplantation|Proportion of subjects who are free from hemodynamic compromise rejection in the absence of a biopsy or histological rejection, From randomization to 18 months post-transplantation|Proportion of subjects who are free from mixed rejection (ACR > ISHLT 2R ACR and AMR > ISHLT AMR 1), From randomization to 18 months post-transplantation|Incidence of acute cellular rejection (ACR) >= International Society of Heart and Lung Transplantation (ISHLT) 2R, From randomization to 18 months post-transplantation|Incidence of acute cellular rejection (ACR) >= International Society of Heart and Lung Transplantation (ISHLT) 3R, From randomization to 18 months post-transplantation|Cumulative incidence of serious infections, including CMV viremia and disease, requiring inpatient/intravenous therapy, From randomization to 18 months post-transplantation|Incidence of post-transplant lymphoproliferative disorder (PTLD), From randomization to 18 months post-transplantation|Incidence of death, From randomization to 18 months post-transplantation|Incidence of re-listing or re-transplantation, From randomization to 18 months post-transplantation|Incidence of malignancies, From randomization to 18 months post-transplantation|Incidence of interruption/discontinuation of study drug, From randomization to 18 months post-transplantation