This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function.The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.
This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function. Research subjects will be recruited from those who were initiated on belatacept at the time of their kidney transplant and have been stable on belatacept therapy for at least 2 years post-transplant and off CNI therapy for at least 6 months. A total of 86 subjects will be randomized in equal numbers, 43 patients in each arm. Enrollment of all 86 patients is expected to be completed within 1.5 years. All patients will be actively followed in the study for 24 months following randomization. The patient participation is projected to last a total of 3.5 years with data analysis to follow. The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
Belatacept is an immunosuppressive medication and will be given as an intravenous infusion at a dose of 5 mg/kg monthly
Abatacept is an immunosuppressive medication and will be given SQ at a dose of 125 mg s.c. weekly
Emory University Hospital (EUH)
Atlanta, Georgia, United States
Change in mean estimated GFR (eGFR) between randomization and 12 months post baseline
Difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.
Time frame: Baseline, 12 months post baseline
Change in eGFR between abatacept and belatacept groups at 24 months
The treatment difference in eGFR between abatacept and belatacept groups at 24 months, using a monthly repeated measures model and a pre-specified acceptable difference, or non-inferiority margin of 5 ml/min/1.73m2.
Time frame: Monthly until 24 months post baseline
Number of subjects with biopsy proven acute rejection: Acute Cellular Rejection (ACR)
Incidence and severity of acute cellular rejection (ACR)
Time frame: 12 months post baseline, 24 months post baseline
Number of subjects with biopsy proven acute rejection: Antibody Mediated Rejection (AMR)
Incidence and severity of antibody mediated rejection (AMR) analyses
Time frame: 12 months post baseline, 24 months post baseline
Number of participants with kidney transplant biopsies post baseline
Number of participants with kidney transplant biopsies post baseline
Time frame: 12 months post baseline, 24 months post baseline
Proportion of subjects treated for ACR/AMR due to clinical suspicion
Proportion of subjects treated for ACR/AMR due to clinical suspicion
Time frame: 12 months post baseline, 24 months post baseline
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Number of subjects with de novo anti-donor human leukocyte antigen (HLA) antibodies
Incidence of de novo anti-donor human leukocyte antigen (HLA) antibodies
Time frame: 12 months post baseline, 24 months post baseline
First occurrence of graft loss or death post baseline
First occurrence of graft loss or death at 6, 12 and 24 months post baseline
Time frame: 12 months post baseline, 24 months post baseline
Number of deaths at 6, 12 and 24 months post baseline
Incidence of death with graft function at 6, 12 and 24 months post baseline
Time frame: 12 months post baseline, 24 months post baseline
Incidence of death-censored graft loss post baseline
Incidence of death-censored graft loss at 12 and 24 months
Time frame: 12 months post baseline, 24 months post baseline
Compliance with patient-administered subcutaneous abatacept
Compliance with patient-administered subcutaneous abatacept
Time frame: 12 months post baseline, 24 months post baseline
Incidence of adverse events
Incidence of adverse events
Time frame: 12 months post baseline, 24 months post baseline
Incidence of serious adverse events
Incidence of serious adverse events
Time frame: 12 months post baseline, 24 months post baseline
Incidence of events of special interest
Incidence of events of special interest, including CMV viremia, BKV viremia, and serious infections
Time frame: 12 months post baseline, 24 months post baseline
Incidence of any malignancy
Incidence of any malignancy including PTLD
Time frame: 12 months post baseline, 24 months post baseline
Incidence of subcutaneous injection site complications
Incidence of subcutaneous injection site complications
Time frame: 12 months post baseline, 24 months post baseline
Proportion of subjects who develop de-novo, anti-HLA donor specific antibody
Proportion of subjects who develop de-novo, anti-HLA donor specific antibody
Time frame: 12 months post baseline, 24 months post baseline