This clinical trial aims to determine whether a bispecific T-cell engager (BiTE) targeting BCMA×CD3 effectively treats chronic active antibody-mediated rejection (cAMR) in kidney transplant recipients. The study also investigates the safety of BiTE in this patient population. The main questions it aims to answer are: 1. Is BiTE safe and tolerable in kidney transplant recipients with cAMR? 2. Can BiTE improve cAMR? (i.e., can it reduce donor-specific antibody levels, ameliorate histological injury on transplant biopsy, and stabilize or improve kidney function by depleting pathogenic B cells and plasma cells?) Researchers will evaluate the effects of BiTE by comparing clinical outcomes before and after treatment in all participants, as this is a single-arm study (all participants receive the same treatment).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Subcutaneous administration of BCMA x CD3 Bispecific Antibody
West China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGIncidence of treatment-emergent adverse events
Throughout the study, safety monitoring will comprise adverse event (AE) surveillance, routine laboratory assessments, and viral polymerase chain reaction (PCR) testing. All AEs and serious adverse events (SAEs) will be classified according to the Medical Dictionary for Regulatory Activities (MedDRA). Documentation of each AE will include both an assessment of its relationship to the investigational product (categorized as either unrelated or related) and a severity grade based on predefined criteria.
Time frame: Through study completion, an average of 1 year
Leukocyte subsets in peripheral blood
Flow cytometric analysis of T, B, and NK (TBNK) cell percentages and absolute counts in peripheral blood.
Time frame: Through study completion, an average of 1 year
Serum immunoglobulin levels
Ig (sub)classes (ELISA, Nephelometry)
Time frame: Through study completion, an average of 1 year
Serum renal function
Measured using an automated analyzer
Time frame: Through study completion, an average of 1 year
HLA antibody detection
HLA antibody profiling, with quantification of donor-specific antibody (DSA) levels. Luminex-based multiplex flow cytometric immunoassay
Time frame: Through study completion, an average of 1 year
Plasma donor-derived cell-free DNA
Detection was performed using fragment analysis combined with digital PCR
Time frame: Through study completion, an average of 1 year
Pathological analysis of renal allograft biopsy
Percutaneous biopsy of the renal allograft was obtained, and histopathological analysis was carried out in accordance with the Banff classification system.
Time frame: At baseline and every 6 months after treatment completion until study completion.
Ultrasound of the renal allograft
Ultrasound examination was performed to evaluate allograft perfusion and to document overall graft morphology.
Time frame: Through study completion, an average of 1 year
Proteinuria: 24 hour urine protein
24-hour urine protein quantifies total protein excretion collected over a 24-hour period.
Time frame: Through study completion, an average of 1 year
Proteinuria: Urine protein to creatinine ratio
Urinary protein excretion in spot urine
Time frame: Through study completion, an average of 1 year
Graft loss
Graft loss as determined by a return to dialysis or death.
Time frame: Through study completion, an average of 1 year
Death
patient survival as assessed by patients vital status.
Time frame: Through study completion, an average of 1 year
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