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.
The subject has given their written informed consent to participate in the study
Recipient of living donor or deceased donor kidney transplant
Age ≥18 years
At least 6 months post-transplantation at randomization
Recipient of multi-organ transplants
De novo or recurrent renal disease that is considered to be the predominant cause of the current graft dysfunction
Active viral infections such as BK virus (BKV), cytomegalovirus (CMV), EBV, COVID-19, hepatitis C virus (HCV) or hepatitis B virus (HBV) infections based on polymerase chain reaction (PCR) testing
Ongoing serious infections as per Investigator's opinion
Parallel
Tocilizumab
DrugTocilizumab is a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor
Change 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).
Composite risk prediction score iBox
Efficacy of the treatment regimen by assessing the iBox score
Incidence of adverse and serious events related to TCZ treatment
Assessments of incidence of any side effects including infectious complications associated with TCZ therapy
Change in Donor-specific anti-HLA antibodies (DSA)
Change in DSA from baseline based on luminex assessments every 12 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
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Vastra Gotaland Region
Lead sponsor
Karolinska University Hospital
Collaborator
Uppsala University Hospital
Collaborator
Skane University Hospital
Collaborator
The Swedish Research Council
Collaborator
Hospital del Mar
Collaborator
Hospital Universitario Doctor Peset
Collaborator
Complexo Hospitalario Universitario de A Coruña
Collaborator
Hospital Universitario Marqués de Valdecilla
Collaborator
