This multi-center study is an investigator-driven randomized controlled parallel group open-label clinical trial designed to evaluate the efficacy of addition of anti-IL-6 antibody tocilizumab (TCZ) to the standard of care (SOC) treatment as compared to the SOC alone in reducing the decline of graft function in kidney transplant recipients with late or chronic antibody-mediated rejection (AMR). A total of 50 recipients will be allocated to receive either TCZ (n=25) added to the standard of care (SOC) or SOC alone (n=25) for a period of 24 months. Patients will be followed for an additional 12 months. Protocol kidney graft biopsies will be performed at 12 and 24 months. The primary outcome is the mean rate of change in graft function as assessed by estimated glomerular filtration rate (eGFR) slope from baseline to 24 months after start of treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Tocilizumab is a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor
Complejo Hospitalario Universitario A Coruña
A Coruña, Spain
NOT_YET_RECRUITINGHospital del Mar
Barcelona, Spain
ACTIVE_NOT_RECRUITINGMarqués de Valdecilla Research Institute
Santander, Spain
NOT_YET_RECRUITINGHospital Universitario Dr. Peset
Valencia, Spain
NOT_YET_RECRUITINGSkåne University Hospital
Malmo, Skåne County, Sweden
RECRUITINGTransplant Center, Sahlgrenska University Hospital
Gothenburg, Vastra Gotaland Regioin, Sweden
RECRUITINGKarolinksa University Hospital
Stockholm, Sweden
RECRUITINGUppsala University Hospital
Uppsala, Sweden
RECRUITINGChange from baseline in eGFR at 24 months
Comparison of eGFR decline (eGFR slope) from baseline at 24 months after start of treatment in the two arms. The eGFR will be assessed by measured creatinine values using MDRD formula in mL/min/1.73m\^2. MDRD formula is based on age, sex, ethnicity, and serum creatinine (in mg/dl) and eGFR values are calculated as follows: GFR in mL/min per 1.73 m\^2 = 175 x Serum Cr\^1.154 x age\^-0.203 x 1.212 (if patient is black) x 0.742 (if female).
Time frame: Baseline and 24 months
Composite risk prediction score iBox
Efficacy of the treatment regimen by assessing the iBox score
Time frame: baseline and upto 24 months
Incidence of adverse and serious events related to TCZ treatment
Assessments of incidence of any side effects including infectious complications associated with TCZ therapy
Time frame: up to 25 months
Change in Donor-specific anti-HLA antibodies (DSA)
Change in DSA from baseline based on luminex assessments every 12 months
Time frame: baseline and up to 36 months
Histologic changes in protocol biopsy
Histologic changes at 12 and 24 months will be compared with those in the baseline biopsies. If the criteria for active AMR are no longer fulfilled in the follow-up biopsies, response to therapy is assumed. The response will be assessed as a yes/no categorical variable. In all biopsies, which still meet the required criteria for active AMR, means of individual Banff lesion scores will be compared between the baseline biopsy and the 12- and 24-months biopsies
Time frame: baseline and up to 24 months
Changes in proteinuria
Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months
Time frame: baseline and up to 36 months
Renal function assessed by measured GFR (mGFR)
Changes from baseline in renal function as assessed by mGFR using iohexol clearance
Time frame: baseline and up to 36 months
Renal function assessed by eGFR
Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR (CKD-EPI)
Time frame: baseline and up to 36 months
Patient survival
Incidence of patient survival at 12, 24 and 36 months after start of treatment
Time frame: up to 36 months
Death-censored graft survival
Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment
Time frame: up to 36 months
Possible change in experienced transplant-specific well-being and symptom burden
Assessed using a validated self-reported questionnaires at baseline and every 12 months
Time frame: upto 36 months
Possible change in experienced perceived threat of the risk of graft rejection
Assessed using a validated self-reported questionnaires at baseline and every 12 months
Time frame: upto 36 months
Possible change in adherence to immunosuppressive medications
Assessed using a validated self-reported questionnaires at baseline and every 12 months
Time frame: upto 36 months
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