Belatacept Therapy for the Failing Renal Allograft

NCT ID: NCT01921218

Last Updated: 2021-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2019-12-12

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.

Conditions

Failing Renal Allograft

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Belatacept (Nulojix) IV

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.

Mycophenolate mofetil

Intervention Type: DRUG

Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later

prednisone

Intervention Type: DRUG

Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis

Control

Calcineurin inhibitor based therapy (cyclosporine or tacrolimus)

Group Type: ACTIVE_COMPARATOR

Calcineurin inhibitor therapy

Intervention Type: DRUG

Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.

Mycophenolate mofetil

Intervention Type: DRUG

Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later

prednisone

Intervention Type: DRUG

Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis

Interventions

Belatacept

Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.

Intervention Type: DRUG

Calcineurin inhibitor therapy

Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.

Intervention Type: DRUG

Mycophenolate mofetil

Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later

Intervention Type: DRUG

prednisone

Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis

Intervention Type: DRUG

Other Intervention Names

Nulojix; tacrolimus; cyclosporine; Cellcept; Deltasone

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Andrew B Adams

OTHER

Sponsor Role: lead

Responsible Party

Andrew B Adams

Assistant Professor of Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Andrew B Adams, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IM103-133

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00060470

Identifier Type: -

Identifier Source: org_study_id