Clinical trial NCT01921218: Belatacept Therapy for the Failing Renal Allograft
Official title: Belatacept Therapy for the Failing Renal Allograft
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Failing Renal Allograft
Keywords: Kidney transplant
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2013-08-13
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The purpose of this study is to test the safety and effectiveness of the medicine belatacept (Nulojix®) in preventing antibodies from forming in people with a failing kidney transplant. Kidney transplant patients take immunosuppression medicines to prevent kidney rejection. When a kidney transplant begins to fail, the immunosuppression medicines are slowly weaned. Once dialysis is started, the immunosuppressant medicines are usually stopped. After immunosuppression is stopped, some people form antibodies. Antibodies are proteins that the immune system makes to protect against harmful foreign substances like bacteria, viruses, or foreign tissues, like a transplant. High levels of antibodies can make it harder to find a kidney donor for that person.

Participants will be randomized into one of the two treatment groups. One group will continue taking their current immunosuppression medicines. The people in the treatment group will be switched to belatacept (Nulojix®). Belatacept (Nulojix®) is an immunosuppression medicine that is approved by the U.S. Food and Drug Administration (the FDA) to prevent rejection in kidney transplant. Participants will stop taking calcineurin inhibitors (either cyclosporine or tacrolimus) or sirolimus but will keep taking other immunosuppression medicines like Cellcept (MMF) or azathioprine (Imuran) and prednisone. These medicines will be slowly weaned and will be stopped if the participant has to start dialysis. Participants will continue taking belatacept (Nulojix®), even while on dialysis.

The study team will test both groups to see how many people in each group develop antibodies.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Donor-specific Antibody Formation
timeFrame: Month 36
Secondary outcomes:
measure: Glomerular Filtration Rate (GFR)
timeFrame: Baseline up to Month 24
measure: Time to Initiation of Dialysis
timeFrame: Up to Year 2
measure: Number of Participants With Anti-human Leukocyte Antigen (HLA) Alloantibodies
timeFrame: Baseline up to Month 36
measure: Number of Infectious Complications
timeFrame: Baseline up to Month 36
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Andrew B Adams, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: