Ignite Creation Date:
2025-12-26 @ 10:57 AM
Ignite Modification Date:
2025-12-26 @ 10:57 AM
Study NCT ID:
NCT03388008
Status:
COMPLETED
Last Update Posted:
2022-11-25
First Post:
2017-12-18
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation
Sponsor:
Washington University School of Medicine
Organization:
Study Overview
Official Title:
A Pilot Randomized Controlled Trial of De Novo Belatacept-Based Immunosuppression in Lung Transplantation
Status:
COMPLETED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a pilot randomized controlled trial examining the feasibility of conducting a large scale randomized controlled trial of belatacept-based immunosuppression in lung transplantation. This pilot study will enroll 40 lung transplant recipients and randomize them to belatacept-based immunosuppression or standard of care. The primary endpoint of the study is the development of donor-specific HLA antibodies after transplantation. All study participants will be followed for a minimum of 12 months after transplantation.
Detailed Description:
Lung transplantation is the ultimate treatment for patients with advanced lung disease. However, long-term outcomes remain disappointing and the median survival after transplantation is approximately 5.5 years. Beyond the first year after transplantation, chronic lung allograft dysfunction is the leading cause of death. The exact mechanisms that lead to chronic lung allograft dysfunction are unclear, but the development of donor-specific HLA antibodies is an independent risk factor. In fact, studies have consistently identified the development of donor-specific HLA antibodies as a significant and independent risk factor for chronic lung allograft dysfunction and mortality after transplantation.
Belatacept is a CTLA4-Ig fusion protein that binds CD80 and CD86 thereby blocking CD28 co-stimulatory signals. Belatacept has been extensively studied in kidney transplantation. In a long-term study, patients treated with Belatacept had better survival than those treated with Cyclosporine. Importantly, Belatacept-treated patients were significantly less likely to develop donor-specific HLA antibodies than Cyclosporine-treated patients. Nonetheless, Belatacept has not been formally evaluated after lung transplantation. The investigators hypothesize that Belatacept-based immunosuppression would result in a lower incidence of donor-specific HLA antibodies and that this would result in better chronic lung allograft dysfunction-free survival after transplantation. Before conducting a large scale randomized controlled trial to test this hypothesis, the investigators plan to conduct the current pilot randomized controlled trial to examine the feasibility of conducting the large scale randomized controlled trial.
The investigators plan to enroll and randomize 40 lung transplant recipients at 2 sites. All recipients will be treated with anti-thymocyte globulin for induction immunosuppression. Those randomized to standard of care immunosuppression will be treated with Tacrolimus, Mycophenolate mofetil, and prednisone. Those randomized to Belatacept-based immunosuppression will be treated with Belatacept, Tacrolimus, and prednisone for the first 89 days; on day 90, Mycophenolate mofetil will be substituted for Tacrolimus and patients will be continued on Belatacept, Mycophenolate mofetil, and prednisone for the remainder of year 1 after transplantation.
Patients in both groups will be monitored closely for episodes of acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection with surveillance bronchoscopy and transbronchial lung biopsies on days 28, 84, 112, 168, 252, and 365 (± 7 days) as part of the sites' routine clinical protocols. In addition, patients will be monitored for the development of donor-specific HLA antibodies with routine blood tests on on days 10 (± 3 days), 28, 56, 84, 112, 168, 252, and 365 (± 7 days).
The primary endpoint of the study is a composite of the development of donor-specific HLA antibodies, re-transplantation, and death. Secondary endpoints include acute cellular rejection, lymphocytic bronchiolitis, antibody-mediated rejection, chronic lung allograft dysfunction, survival, cytomegalovirus infection, bacterial infection, community-acquired respiratory viral infection, chronic kidney disease stage 3, malignancy, hypertension, diabetes, and hypercholesterolemia.
Belatacept is a CTLA4-Ig fusion protein that binds CD80 and CD86 thereby blocking CD28 co-stimulatory signals. Belatacept has been extensively studied in kidney transplantation. In a long-term study, patients treated with Belatacept had better survival than those treated with Cyclosporine. Importantly, Belatacept-treated patients were significantly less likely to develop donor-specific HLA antibodies than Cyclosporine-treated patients. Nonetheless, Belatacept has not been formally evaluated after lung transplantation. The investigators hypothesize that Belatacept-based immunosuppression would result in a lower incidence of donor-specific HLA antibodies and that this would result in better chronic lung allograft dysfunction-free survival after transplantation. Before conducting a large scale randomized controlled trial to test this hypothesis, the investigators plan to conduct the current pilot randomized controlled trial to examine the feasibility of conducting the large scale randomized controlled trial.
The investigators plan to enroll and randomize 40 lung transplant recipients at 2 sites. All recipients will be treated with anti-thymocyte globulin for induction immunosuppression. Those randomized to standard of care immunosuppression will be treated with Tacrolimus, Mycophenolate mofetil, and prednisone. Those randomized to Belatacept-based immunosuppression will be treated with Belatacept, Tacrolimus, and prednisone for the first 89 days; on day 90, Mycophenolate mofetil will be substituted for Tacrolimus and patients will be continued on Belatacept, Mycophenolate mofetil, and prednisone for the remainder of year 1 after transplantation.
Patients in both groups will be monitored closely for episodes of acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection with surveillance bronchoscopy and transbronchial lung biopsies on days 28, 84, 112, 168, 252, and 365 (± 7 days) as part of the sites' routine clinical protocols. In addition, patients will be monitored for the development of donor-specific HLA antibodies with routine blood tests on on days 10 (± 3 days), 28, 56, 84, 112, 168, 252, and 365 (± 7 days).
The primary endpoint of the study is a composite of the development of donor-specific HLA antibodies, re-transplantation, and death. Secondary endpoints include acute cellular rejection, lymphocytic bronchiolitis, antibody-mediated rejection, chronic lung allograft dysfunction, survival, cytomegalovirus infection, bacterial infection, community-acquired respiratory viral infection, chronic kidney disease stage 3, malignancy, hypertension, diabetes, and hypercholesterolemia.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: