Antibody-mediated Rejection, Antibody-Mediated Rejection (AMR)
Conditions
Brief summary
The goal of this clinical trial is to: a. To evaluate the safety and efficacy of sequential daratumumab followed by telitacicept in kidney transplant recipients with active/chronic active ABMR in participants aged 18-70 years, time since kidney transplantation ≥180 days, meeting Banff 2022 criteria for active/chronic active ABMR, and eGFR ≥20 mL/min/1.73m² (2021 CKD-EPI formula). The main questions it aims to answer are: What is the incidence of CTCAE v6.0 grade ≥3 adverse events during treatment? What are the changes from baseline in urine protein-to-creatinine ratio (UPCR), eGFR, urine albumin-to-creatinine ratio (UACR), and donor-specific antibody (DSA) mean fluorescence intensity (MFI) during the follow-up period? If there is a comparison group: Not applicable (single-arm study). Participants will: Receive the study-specified sequential regimen (daratumumab followed by telitacicept).Attend scheduled follow-up visits at weeks 4, 8, 12, 16, 20, 24, 36, and 52.Undergo laboratory tests (including UPCR, eGFR, UACR, DSA MFI, etc.) at each follow-up visit.During scheduled follow-up visits, investigators will promptly assess participants for the occurrence of adverse events (AEs), the grade of AEs (according to CTCAE v6.0), as well as efficacy outcomes.
Interventions
Methylprednisolone 250-500 mg once daily is given on Days 0, 1, and 2 (total of 3 doses)
DRUGDaratumumab
Daratumumab (DARA) 1800 mg is administered starting on Day 4, followed by 1800 mg every 2 weeks (q2w) through Week 12.
DRUGTelitacicept
Telitacicept (TACI) 160 mg once weekly (qw) is given from Week 12 to Week 52.
Sponsors
First Affiliated Hospital, Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. 18 years ≤ Age ≤ 70 years. 2. Kidney transplant recipients meeting Banff 2022 criteria for active/chronic active ABMR: Diagnosis is based on kidney biopsy and HLA-DSA. Subjects may also be enrolled if they have concurrent other histopathological findings that are determined to be the primary cause of renal dysfunction along with ABMR. (Kidney biopsy must be performed within 90 days before screening or during the screening period). 3. Time since kidney transplantation ≥ 180 days. 4. Estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73m² (CKD-EPI formula). 5. HLA Class I or Class II antibody with MFI \> 1000 (pre-existing or de novo DSA). 6. Recipient of a living-related or deceased donor kidney. 7. Patients of childbearing potential (including male patients with female partners of childbearing potential) must agree to use effective contraception from the time of signing the informed consent form until 4 months after the last dose of the investigational product. 8. Voluntary provision of written informed consent and ability to cooperate with follow-up visits.
Exclusion criteria
1. Multi-organ transplant recipient. 2. ABO blood group incompatibility. 3. Pathology indicates concurrent lesions that are the primary cause of renal dysfunction: T-cell mediated rejection (TCMR) grade 1 or above, thrombotic microangiopathy (TMA), BK virus-associated nephropathy, de novo or recurrent glomerulonephritis. 4. Pregnant or breastfeeding women. 5. Intolerance to the triple immunosuppressive regimen of tacrolimus + mycophenolic acid + glucocorticoids. 6. Patients with abnormal liver function: total bilirubin \> 2 × upper limit of normal (ULN), or alanine aminotransferase (ALT), aspartate aminotransferase (AST) \> 2.5 × ULN. 7. Patients with abnormal hematology: platelet count \< 100×10⁹/L. or white blood cell count \< 3×10⁹/L. or neutrophil count \< 1.5×10⁹/L. 8. Serum globulin \< 4 g/L. 9. Patients with active bacterial, fungal, or viral infections, such as herpes zoster, HIV, active tuberculosis, active hepatitis B or C. 10. Latent tuberculosis (positive tuberculin skin test or interferon-gamma release assay without clinical or radiographic evidence of active disease). 11. Active malignancy, precluding intensive immunosuppressive therapy. 12. History of alcohol or illicit drug abuse. 13. History of severe medical or psychiatric illness. 14. Use of acute rejection treatment (e.g., methylprednisolone pulse therapy, anti-thymocyte globulin (ATG)) or plasma exchange (PLEX) within 3 months before screening. 15. Prior use of CD38 monoclonal antibody, BAFF inhibitor, BAFF/APRIL inhibitor, or other drugs with the same target as the investigational products. 16. Use of CD20 monoclonal antibody, high-dose IVIG (1-2 g/kg), IL6/IL-6R antibody, etc., within 6 months before screening. 17. Live vaccination within 6 weeks before screening. 18. Participation in other clinical trials within 6 months before screening. 19. Any other reason deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of CTCAE v6.0 grade ≥ 3 adverse events (AEs) during the Phase A (0-24 weeks) follow-up period. | From enrollment to the end of treatment at 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of AEs during the follow-up period (Phase B: 25-52 weeks). | From enrollment to the end of treatment at 52 weeks |
| Change in eGFR from baseline during the follow-up period | From enrollment to the of treatment at 24 weeks and 52 weeks |
Countries
China
Outcome results
None listed