Trial Outcomes & Findings for Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation (NCT NCT03388008)

Last Updated: 2022-11-25

Results Overview

The Outcome Measure is a composite primary endpoint of the development of donor-specific HLA antibodies, re-transplantation, or death. Testing for donor-specifc HLA antibodies was performed at study-specified time points using the single antigen bead assay at the study core lab. Donor-specific HLA antibodies were defined as reactivity with a mean fluorescence intensity (MFI) ≥ 2,000.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

365 days

Results posted on

2022-11-25

Participant Flow

Participants were recruited at 2 centers (Washington University in St. Louis and Houston Methodist Hospital) between 12/2019 and 5/2021.

Participant milestones

Participant milestones
Measure	Standard of Care Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365	Belatacept-based Immunosuppression Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
Overall Study STARTED	14	13
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care n=14 Participants Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365	Belatacept-based Immunosuppression n=13 Participants Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365	Total n=27 Participants Total of all reporting groups
Age, Continuous	59.5 years STANDARD_DEVIATION 11.8 • n=5 Participants	57.8 years STANDARD_DEVIATION 7.5 • n=7 Participants	58.7 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants
Diagnosis Interstitial Lung Disease	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Diagnosis COPD	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Diagnosis Pulmonary Arterial Hypertension	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Diagnosis Other	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Operation Bilateral lung transplant	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Operation Single lung transplant	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 365 days

Outcome measures

Outcome measures
Measure	Standard of Care n=14 Participants Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365	Belatacept-based Immunosuppression n=13 Participants Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
Donor-specific HLA Antibodies, Re-transplantation, or Death Re-transplantation	0 participants	0 participants
Donor-specific HLA Antibodies, Re-transplantation, or Death Death	0 participants	5 participants
Donor-specific HLA Antibodies, Re-transplantation, or Death Donor-specific HLA antibodies	3 participants	3 participants

Adverse Events

Standard of Care

Serious events: 10 serious events

Other events: 12 other events

Deaths: 0 deaths

Belatacept-based Immunosuppression

Serious events: 10 serious events

Other events: 13 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Ramsey Hachem, MD

Washington University in St. Louis

Phone: (314) 454-7953

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Standard of Care n=14 participants at risk Tacrolimus + Mycophenolate mofetil + prednisone from day 0 through day 365 Tacrolimus: Tacrolimus will be dosed enterally or sublingually within 48 hours of transplantation and the dose will be adjusted to target a trough blood level of 8-15 ng/ml ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365	Belatacept-based Immunosuppression n=13 participants at risk Belatacept + Tacrolimus + prednisone from day 0 through day 89, then Belatacept + Mycophenolate mofetil + prednisone from day 90 through day 365 Belatacept: Belatacept will be dosed at 10 mg/kg of actual body weight on days 0, 7, 14, 28, 56, and 84 then at 5 mg/kg on day 112 and every 28 days through day 364 (i.e., on days 140, 168, 196, 224, 252, 280, 308, 336, and 364) ATG: Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation Mycophenolate Mofetil: Mycophenolate mofetil will be dosed at 1000 mg twice daily (or if the enteric coated formulation is used, this will be dosed at 720 mg twice daily. In the standard of care arm, mycophenolate mofetil will be initiated on day 0 after transplantation, whereas in the belatacept-based immunosuppression arm, mycophenolate mofetil will be initiated on day 90 after transplantation Methylprednisolone: Methylprednisolone 500 mg will be given intravenously before perfusion of the allograft during the transplant procedure, then methylprednisolone 0.5 mg/kg will be given intravenously twice daily for 6 total doses Prednisone: Prednisone will be dosed at 0.5 mg/kg orally daily through day 14, then 0.2 mg/kg orally daily through day 30, then 0.1 mg/kg daily through day 180, then 5 mg daily through day 365
Vascular disorders Venous Thromboembolism	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	15.4% 2/13 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Respiratory, thoracic and mediastinal disorders Respiratory failure	28.6% 4/14 • Number of events 4 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	46.2% 6/13 • Number of events 12 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Infections and infestations COVID-19 infection	21.4% 3/14 • Number of events 3 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	15.4% 2/13 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Infections and infestations Surgical site infection	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Infections and infestations Pneumonia	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Infections and infestations Cytomegalovirus infection	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	15.4% 2/13 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Cardiac disorders Atrial fibrillation	14.3% 2/14 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Immune system disorders Acute rejection	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Renal and urinary disorders Acute kidney injury	14.3% 2/14 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Nervous system disorders Syncope	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Vascular disorders Limb ischemia	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Gastrointestinal disorders Nausea and vomiting	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	15.4% 2/13 • Number of events 2 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Gastrointestinal disorders Dysphagia	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Infections and infestations Parainfluenza virus infection	7.1% 1/14 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	0.00% 0/13 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Nervous system disorders Headache	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Post-transplant lymphoproliferative disease	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Musculoskeletal and connective tissue disorders Multiple fractures	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.
Respiratory, thoracic and mediastinal disorders Hemothorax	0.00% 0/14 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.	7.7% 1/13 • Number of events 1 • Adverse events were collected over 14 months after randomization. However, not all participants have completed 14 months of follow-up at this time.