This study is a prospective, open-label, two-arm exploratory clinical trial aimed at evaluating the safety and efficacy of Bispecific T-cell Engager (BiTE) therapies in refractory, highly sensitized kidney transplant candidates. Patients with end-stage renal disease (ESRD) who have a calculated panel reactive antibody (cPRA) ≥ 90% and have waited for a transplant for over 5 years, despite receiving standard desensitization therapies (e.g., IVIG, plasmapheresis, rituximab), will be enrolled.
A total of 20 participants will be randomized in a 1:1 ratio to receive either Blinatumomab (a CD19×CD3 BiTE) or Teclistamab (a BCMA×CD3 BiTE). The primary objective is to evaluate the desensitization response rate, defined as the reduction of cPRA to \< 20% or by ≥ 50% from baseline, assessed at multiple time points up to 1 year post-treatment. Secondary objectives include assessing the safety profile (such as the incidence of Cytokine Release Syndrome \[CRS\] and neurotoxicity), the extent of CD19+ B cell depletion, and the proportion of participants who successfully undergo kidney transplantation within 1 year.
Male or female participants aged 18 to 65 years.
Diagnosis of end-stage kidney disease and being evaluated for or awaiting kidney transplantation.
Calculated panel-reactive antibody level (cPRA) ≥90% and a kidney transplant waiting time of ≥5 years.
Previous treatment with a conventional desensitization regimen based on intravenous immunoglobulin and/or plasma exchange, with or without rituximab, with traceable medical records.
Inability to understand or comply with the study protocol or follow-up schedule.
Known or suspected hereditary complement deficiency.
Clinically significant central nervous system disease, including epilepsy, psychotic disorder, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, or cranial neuropathy requiring intervention.
AST, ALT, or GGT >3 times the upper limit of normal, or alkaline phosphatase or total bilirubin >1.5 times the upper limit of normal.