Antibody Mediated Rejection After Kidney Transplantation
Conditions
Keywords
Kidney Transplant Recipients with Chronic Active Antibody-Mediated Rejection, bispecific antibody
Brief summary
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).
Interventions
Subcutaneous administration of BCMA x CD3 Bispecific Antibody
Sponsors
Turun Song
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Functioning living or deceased donor allograft after ≥180 days post-transplantation. 3. eGFR ≥20 ml/min/1.73 m2 (CKD-EPI formula). 4. HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA). 5. Biopsy-confirmed chronic active antibody-mediated rejection (cAMR) according to the Banff 2019 criteria. 6. Voluntarily signed informed consent, with willingness and ability to adhere to regular follow-up and complete collection of all study-related information.
Exclusion criteria
1. Patients actively participating in another clinical trial. 2. Age \<18 years. 3. Pregnancy, lactation, or planned pregnancy during the study period. 4. Multi-organ recipients, e.g., patients with concurrent or prior bone marrow transplantation or other organ transplantation. 5. Kidney transplantation biopsy combined with one of the following results: A. T-cell-mediated rejection classified Banff grade ≥I. B. De novo or recurrent severe thrombotic microangiopathy. C. Polyoma virus nephropathy, De novo or recurrent glomerulonephritis. 6. Previous treatment with any BCMA-targeted agent, including monoclonal antibodies (e.g., ADCs, bispecifics) or CAR-T cell therapy. 7. Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) ≤3 months before study treatment. 8. Total bilirubin \>2×the upper limit of normal \[ULN\], alanine transaminase and aspartate aminotransferase \>2.5×ULN 9. Haemoglobin \<8 g/dL 10. Thrombocytopenia: Platelets \<100 G/L 11. Leukopenia: Leukocytes \<3 G/L 12. Neutropenia: Neutrophils \< 1.5 G/L 13. Hypogammaglobulinemia: Serum IgG \<400 mg/dL 14. Active viral, bacterial, or fungal infection precluding intensified immunosuppression. 15. Active malignant disease precluding intensified immunosuppressive therapy. 16. Latent or active tuberculosis. 17. Administration of a live vaccine within 6 weeks of screening. 18. Central nervous system (CNS) disorders, including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or CNS vasculitis, visual disturbances, cranial neuropathy requiring intervention, etc. 19. History of alcohol or illicit substance abuse 20. Serious medical or psychiatric illness likely to interfere with participation in the study. 21. Presence of any other clinically significant medical history or current disease that, in the judgment of the investigator, would compromise subject safety, impede completion of the study protocol, or compromise the assessment of safety and efficacy. .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | Through study completion, an average of 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Leukocyte subsets in peripheral blood | Through study completion, an average of 1 year | Flow cytometric analysis of T, B, and NK (TBNK) cell percentages and absolute counts in peripheral blood. |
| Serum immunoglobulin levels | Through study completion, an average of 1 year | Ig (sub)classes (ELISA, Nephelometry) |
| Serum renal function | Through study completion, an average of 1 year | Measured using an automated analyzer |
| HLA antibody detection | Through study completion, an average of 1 year | HLA antibody profiling, with quantification of donor-specific antibody (DSA) levels. Luminex-based multiplex flow cytometric immunoassay |
| Plasma donor-derived cell-free DNA | Through study completion, an average of 1 year | Detection was performed using fragment analysis combined with digital PCR |
| Pathological analysis of renal allograft biopsy | At baseline and every 6 months after treatment completion until study completion. | Percutaneous biopsy of the renal allograft was obtained, and histopathological analysis was carried out in accordance with the Banff classification system. |
| Ultrasound of the renal allograft | Through study completion, an average of 1 year | Ultrasound examination was performed to evaluate allograft perfusion and to document overall graft morphology. |
| Proteinuria: 24 hour urine protein | Through study completion, an average of 1 year | 24-hour urine protein quantifies total protein excretion collected over a 24-hour period. |
| Proteinuria: Urine protein to creatinine ratio | Through study completion, an average of 1 year | Urinary protein excretion in spot urine |
| Graft loss | Through study completion, an average of 1 year | Graft loss as determined by a return to dialysis or death. |
| Death | Through study completion, an average of 1 year | patient survival as assessed by patients vital status. |
Countries
China
Contacts
CONTACTYunfei Xiao, Ph.D
Outcome results
None listed