Belatacept Therapy for the Failing Renal Allograft

• Status: Completed
• Trial end date: 2019-12-12
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA). Patients must be eligible to get a second transplant. They must have completed or be actively undergoing evaluation for re-listing for a second transplant. Patients will be randomized to either convert to belatacept or continue on calcineurin inhibitor-based therapy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Andrew B Adams; Andrew B Adams, MD, PhD
• Collaborator: Bristol-Myers Squibb
• Treatments: Abatacept; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Mycophenolate mofetil; Mycophenolic Acid; Prednisone; Tacrolimus

Criteria

Inclusion Criteria:

• Signed written informed consent

• Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who now has impaired renal allograft function with:

• Estimated glomerular filtration rate (GFR) < 35 with a decline in GFR of > 10% in the 12 months prior to enrollment and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy (IF/TA) OR

• Estimated GFR persistently < 20 ml/min over the 6 month period prior to enrollment absent other causes for graft dysfunction, and deemed to have a failing allograft by the patient's transplant nephrologist

• On a maintenance immunosuppressive regimen that includes calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) or sirolimus and at least

• MMF of a dose of at least 1 gm/day or comparable dose of azathioprine OR

• Prednisone at a dose of at least 5 mg/day

• Men and women, ages 18 to 70, inclusive

Exclusion Criteria:

• Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug.

• Women who are pregnant or breastfeeding.

• Women with a positive pregnancy test.

• Sexually active fertile men not using effective birth control if their partners are WOCBP.

• Subjects who are Epstein-Barr Virus (EBV) seronegative.

• Subjects with any prior solid organ (e.g., heart, liver, pancreas) or cell (e.g., islet, bone marrow) transplant other than a renal allograft. Exception may be made for recipient of a simultaneous kidney-pancreas transplant who had previously experienced graft loss of the pancreas allograft due to thrombosis or rejection.

• Subjects with presence of donor specific antibody at the time of enrollment

• Subjects who have a recent history (within 1 yr) of biopsy proven acute rejection > Banff grade Ia

• Subjects who have a living donor identified for re-transplant within 3 months

• Subjects with a history of post-transplant lymphoproliferative disease (PTLD)

• Subjects at risk for tuberculosis (TB)

• Subjects with a history of cancer within the past 3 years, other than non-melanoma skin cancer(s)

• Subjects with a positive BK virus serum polymerase chain reaction (PCR) > 20,000 copies at the time of enrollment OR history of biopsy-proven BK nephropathy within the year prior to enrollment.

• Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations

• Subjects who have difficult intravenous access or other reasons that would likely preclude the ability to receive long-term intravenous infusions

• Hypersensitivity to any medications that will be used in the protocol

• Subjects who have used any investigational drug within the 30 days prior to anticipated enrollment

• Subjects currently receiving belatacept as part of their maintenance immunosuppressive regimen

• Prisoners, or subjects who are involuntarily incarcerated.

• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.