Bela 8 Week Dosing

Phase 4

Completed

Conditions: Kidney Transplantation

Interventions: Drug: Belatacept

Registration Number: NCT02560558

Lead Sponsor: Emory University

Brief Summary: The purpose of this study is to transition patients who have been stable on Belatacept for one year after kidney transplant from standard 4-week to an investigational 8-week belatacept dosing schedule. The investigators hypothesize that renal function and acute rejection rates will be non-inferior with 8-week belatacept dosing.

Detailed Description: The current dosing protocol for patients who have undergone a kidney transplant requires that Belatacept be given as an infusion every 4 weeks. The investigator wants to assess if the patients who have been stable for one year after transplant can be safely transitioned to an 8-week Belatacept infusion schedule. Renal function and any episodes of acute rejection will be closely monitored.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 166

Inclusion Criteria

Adult (age ≥18 years currently),
First-time renal transplant recipients of either living donor or deceased donor,
1. who were initiated on belatacept at the time of transplant and
2. are at least one year post-transplant and off CNI therapy for at least 6 months.
Patients at low immunologic risk, defined as
1. patients with a first transplant who have a PRA < 50 against class I and class II antigens,
2. no DSA (donor-specific antibodies),
3. who have not had more than one episode of rejection, and
4. no episodes of rejection within the last 6 months prior to enrollment, and
5. no rejection with a grade of IIB or above.

Exclusion Criteria

Not first renal transplant, or multi-organ transplant recipient
History of greater than one episode of biopsy-proven acute rejection, or of rejection of Banff 97 grade IIB or greater, or rejection within the last 6 months.
Pregnancy (women of childbearing potential must use adequate contraception during study)
Unwilling to receive all belatacept infusions at the Emory Transplant Center
Calculated Glomerular Filtration Rate (GFR) less than 35.
Serum creatinine at enrollment over 30% higher than 3 months (±4 weeks) prior to randomization
HbA1C greater than 8 at enrollment
Recent history of significant proteinuria (protein/Cr ratio >1)
Non-standard belatacept dosing (e.g. dose other than 5 mg belatacept/kg body weight)
Cellcept dose less than 500 mg po bid.
Prednisone dose greater than 5mg po qd within 3 months of randomization
Patients not currently taking prednisone
Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization
Evidence of Cytomegalovirus (CMV) viremia or clinical CMV infection within last 3 months.
Polyomavirus BK PCR (polymerase chain reaction) load greater then 4.3 (copy number greater than 20,0000) within 3 months of randomization
Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required)
Known HIV (human immunodeficiency virus infection) (testing not required)
Presence of donor specific antibody by Luminex single antigen assessment, or panel reactivity (PRA) above 50%.
History of substance abuse or psychiatric disorder not compatible with study adherence and follow up.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Belatacept 8-weekly	Belatacept	Subjects who are stable on belatacept therapy at least one year after a renal transplant will receive belatacept infusion intravenously (IV) at 5 mg/kg every 8 weeks.
Belatacept 4-weekly	Belatacept	Subjects who are stable on belatacept therapy at least one year after a renal transplant will receive belatacept infusion intravenously (IV) at 5 mg/kg every 4 weeks.

Primary Outcome Measures

Name	Time	Method
Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline	12 months from baseline	The mean estimated Glomerular Filtration Rate (eGFR) will be calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine measurements and the patient's age, gender, and race. An eGFR below 60 ml/min/1.73 m\^2 indicates lower renal function.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline	6 months post baseline, 12 months post baseline	The number of occurrences of transplant rejection at 6 months and 12 months from baseline will be recorded.
Number of Deaths at 6 Months and 12 Months Post Baseline	6 months post baseline, 12 months post baseline	The total number of subject deaths at 12 months from baseline will be recorded.
Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline	6 months post baseline, 12 months from baseline	The total number of subjects who experienced death censored graft loss at 6 months and 12 months from baseline will be recorded.
Cost Analysis	At 12 months from baseline	The mean total cost of infusions received by each subject and those associated with round trip travel to the Emory Transplant Center (ETC) will be estimated using the distance between the residential addresses of subjects and the ETC.
Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline	6 months post baseline, 12 months post baseline	The number of subjects with Grade IIB and higher severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells.
Number of Clinic Visits	At 12 months from baseline	The number of clinic visits by the subjects at the end of 12 months from baseline will be recorded.
Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline	6 months post baseline, 12 months post baseline	The number of subjects with Grade IIA and lower severity of rejection on the Banff 97 diagnostic categories will be recorded. The severity of acute rejections will be graded based on histopathological findings; Grade IA= significant interstitial infiltration and moderate tubulitis; Grade IB= significant interstitial infiltration and severe tubulitis; Grade IIA= mild to moderate intimal arteritis; Grade IIB= severe intimal arteritis and Grade III= transmural arteritis and/or fibrinoid change and necrosis of cells.
Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline	6 moths post baseline, 12 months post baseline	The number of subjects who have circulating human leukocyte antigen donor specific antibodies (HLA DSA) at 12 months from baseline will be recorded.
Number of Subjects Needing Hospitalizations	At 12 months from baseline	The number of subjects who had hospitalizations at the end of 12 months from baseline will be recorded
Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline	12 months post baseline	The number of subjects needing transplant biopsies at 12 months from baseline will be recorded.