Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation
Condition: Lung Transplant Rejection; Antibody-mediated Rejection
Intervention: Belatacept; Tacrolimus; ATG; Mycophenolate Mofetil; Methylprednisolone; Prednisone
Intervention description: 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); 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; Anti-thymocyte globulin will be dosed intravenously at 3 mg/kg divided into 3 daily doses starting on day 0 after transplantation; 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 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 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
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Methylprednisolone; Methylprednisolone Hemisuccinate; Abatacept; Tacrolimus; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Study participants will be randomized to 1 of 2 arms: Belatacept-based immunosuppression or standard of care immunosuppression
Masking: Single (Outcomes Assessor)
Masking description: Investigators examining lung biopsy results and blood for the development of donor-specific HLA antibodies will be blinded to study participants' treatment arm assignment.
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: donor-specific HLA antibodies; lung transplantation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provided written informed consent for study participation

          -  Underwent single or bilateral lung transplantation

          -  Negative urine pregnancy test for women of child bearing potential and willingness to
             use highly-effective contraception

        Exclusion Criteria:

          -  Requiring invasive mechanical ventilation immediately before transplantation

          -  Requiring extracorporeal life support (ECLS) (i.e., ECMO) immediately before
             transplantation

          -  Received treatment to deplete HLA antibodies before transplantation to improve the
             possibility of transplantation

          -  Having DSA immediately before transplantation (i.e., positive virtual crossmatch)

          -  Listed for multi-organ transplant (e.g., heart-lung, liver-lung, kidney-lung)

          -  Pregnant or breast-feeding

          -  Active infection with Hepatitis B or C virus

          -  Active infection with human immunodeficiency virus (HIV)

          -  Chronic infection with Burkholderia cepacia complex before transplantation

          -  Epstein Barr Virus (EBV) seronegative status

          -  Participation in another interventional clinical trial

          -  Allograft dysfunction requiring ECMO support after transplantation

          -  Delayed chest closure after transplantation

          -  Severe coagulopathy and significant bleeding in the opinion of the PI

          -  Any condition that in the opinion of the site PI introduces undue risk by
             participating in this study