- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT07689578
Safety and Efficacy of the Bispecific T-Cell Engager (BiTE) in Kidney Transplant Recipients With Chronic Active Antibody-Mediated Rejection
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:
- Is BiTE safe and tolerable in kidney transplant recipients with cAMR?
- 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).
Panoramica dello studio
Stato
Intervento / Trattamento
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 4
Contatti e Sedi
Contatto studio
- Nome: Yunfei Xiao, Ph.D
- Numero di telefono: +86 28 85422925
- Email: xiaoyunfeix@163.com
Luoghi di studio
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Sichuan
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Chengdu, Sichuan, Cina, 610041
- Reclutamento
- West China Hospital, Sichuan University
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
Inclusion Criteria:
- Age ≥18 years.
- Functioning living or deceased donor allograft after ≥180 days post-transplantation.
- eGFR ≥20 ml/min/1.73 m2 (CKD-EPI formula).
- HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA).
- Biopsy-confirmed chronic active antibody-mediated rejection (cAMR) according to the Banff 2019 criteria.
- Voluntarily signed informed consent, with willingness and ability to adhere to regular follow-up and complete collection of all study-related information.
Exclusion Criteria:
- Patients actively participating in another clinical trial.
- Age <18 years.
- Pregnancy, lactation, or planned pregnancy during the study period.
- Multi-organ recipients, e.g., patients with concurrent or prior bone marrow transplantation or other organ transplantation.
- 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.
- Previous treatment with any BCMA-targeted agent, including monoclonal antibodies (e.g., ADCs, bispecifics) or CAR-T cell therapy.
- Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) ≤3 months before study treatment.
- Total bilirubin >2×the upper limit of normal [ULN], alanine transaminase and aspartate aminotransferase >2.5×ULN
- Haemoglobin <8 g/dL
- Thrombocytopenia: Platelets <100 G/L
- Leukopenia: Leukocytes <3 G/L
- Neutropenia: Neutrophils < 1.5 G/L
- Hypogammaglobulinemia: Serum IgG <400 mg/dL
- Active viral, bacterial, or fungal infection precluding intensified immunosuppression.
- Active malignant disease precluding intensified immunosuppressive therapy.
- Latent or active tuberculosis.
- Administration of a live vaccine within 6 weeks of screening.
- Central nervous system (CNS) disorders, including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or CNS vasculitis, visual disturbances, cranial neuropathy requiring intervention, etc.
- History of alcohol or illicit substance abuse
- Serious medical or psychiatric illness likely to interfere with participation in the study.
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.
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Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Bispecific T cell engager treatment group
BiTE (BCMA x CD3 Bispecific Antibody)
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Subcutaneous administration of BCMA x CD3 Bispecific Antibody
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Incidence of treatment-emergent adverse events
Lasso di tempo: 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.
|
Through study completion, an average of 1 year
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Leukocyte subsets in peripheral blood
Lasso di tempo: 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.
|
Through study completion, an average of 1 year
|
|
Serum immunoglobulin levels
Lasso di tempo: Through study completion, an average of 1 year
|
Ig (sub)classes (ELISA, Nephelometry)
|
Through study completion, an average of 1 year
|
|
Serum renal function
Lasso di tempo: Through study completion, an average of 1 year
|
Measured using an automated analyzer
|
Through study completion, an average of 1 year
|
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HLA antibody detection
Lasso di tempo: 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
|
Through study completion, an average of 1 year
|
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Plasma donor-derived cell-free DNA
Lasso di tempo: Through study completion, an average of 1 year
|
Detection was performed using fragment analysis combined with digital PCR
|
Through study completion, an average of 1 year
|
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Pathological analysis of renal allograft biopsy
Lasso di tempo: At baseline and every 6 months after treatment completion until study completion.
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Percutaneous biopsy of the renal allograft was obtained, and histopathological analysis was carried out in accordance with the Banff classification system.
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At baseline and every 6 months after treatment completion until study completion.
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Ultrasound of the renal allograft
Lasso di tempo: Through study completion, an average of 1 year
|
Ultrasound examination was performed to evaluate allograft perfusion and to document overall graft morphology.
|
Through study completion, an average of 1 year
|
|
Proteinuria: 24 hour urine protein
Lasso di tempo: Through study completion, an average of 1 year
|
24-hour urine protein quantifies total protein excretion collected over a 24-hour period.
|
Through study completion, an average of 1 year
|
|
Proteinuria: Urine protein to creatinine ratio
Lasso di tempo: Through study completion, an average of 1 year
|
Urinary protein excretion in spot urine
|
Through study completion, an average of 1 year
|
|
Graft loss
Lasso di tempo: Through study completion, an average of 1 year
|
Graft loss as determined by a return to dialysis or death.
|
Through study completion, an average of 1 year
|
|
Death
Lasso di tempo: Through study completion, an average of 1 year
|
patient survival as assessed by patients vital status.
|
Through study completion, an average of 1 year
|
Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Pubblicazioni generali
- Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel M. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020 Sep;20(9):2318-2331. doi: 10.1111/ajt.15898. Epub 2020 May 28.
- Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martinez-Lopez J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.
- Leon J, Aubert O, Devriese M, Alameda F, Charbonnier S, Fourgeaud J, Blein T, Nguyen TN, Troger A, Chhun S, Roelens M, Usureau C, Gons C, Roger C, Burger C, Le Stang MB, Cotteret C, Timsit MO, Fillatreau S, Rabant M, Taupin JL, Talbot A, Suarez F, Anglicheau D, Zuber J. B-cell maturation antigen-Targeted T-cell Engager Therapy Combined with B-cell Depletion for Treatment of Refractory HLA Sensitization. Kidney Int. 2026 Jun;109(6):1148-1154. doi: 10.1016/j.kint.2026.01.020. Epub 2026 Feb 13.
- Gregg-Garcia R, Abonour R, Suvannasankha A. Bispecific T-cell engagers for relapsed/refractory multiple myeloma after solid organ transplantation: A case series. J Investig Med. 2026 Apr;74(3):289-293. doi: 10.1177/10815589251364807. Epub 2025 Jul 28.
- Forgeard N, Elessa D, Carpinteiro A, Belhadj K, Minnema M, Roussel M, Huart A, Javaugue V, Pascal L, Royer B, Talbot A, Gounot R, Hegenbart U, Schonland S, Karlin L, Harel S, Kastritis E, Bridoux F, Jaccard A, Arnulf B. Teclistamab in relapsed or refractory AL amyloidosis: a multinational retrospective case series. Blood. 2024 Feb 22;143(8):734-737. doi: 10.1182/blood.2023022937. No abstract available.
- Schreiber S, Al-Dubai M, Vielhaber S, Lefterova L, Dietrich S, Ruck T, Meuth S, Walther D, Mougiakakos D. Effective use of BCMA-targeting bispecific T cell-engaging antibody in treatment-refractory LRP4+ myasthenia gravis. Mol Ther. 2025 Sep 3;33(9):4130-4134. doi: 10.1016/j.ymthe.2025.06.029. Epub 2025 Jun 17.
- Usmani SZ, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Rosinol L, Chari A, Bhutani M, Karlin L, Benboubker L, Pei L, Verona R, Girgis S, Stephenson T, Elsayed Y, Infante J, Goldberg JD, Banerjee A, Mateos MV, Krishnan A. Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021 Aug 21;398(10301):665-674. doi: 10.1016/S0140-6736(21)01338-6. Epub 2021 Aug 10.
- Baines AC, Kanapuru B, Zhao J, Price LSL, Zheng N, Konicki R, Manning ML, Gehrke BJ, Theoret MR, Gormley NJ. FDA Approval Summary: Teclistamab-A Bispecific CD3 T-Cell Engager for Patients with Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2024 Dec 16;30(24):5515-5520. doi: 10.1158/1078-0432.CCR-24-1872.
- de Nattes T, Camus V, Francois A, Dallet G, Ferrand C, Guerrot D, Lemoine M, Morin F, Thieblemont C, Veresezan EL, Candon S, Latouche JB, Bertrand D. Kidney Transplant T Cell-Mediated Rejection Occurring After Anti-CD19 CAR T-Cell Therapy for Refractory Aggressive Burkitt-like Lymphoma With 11q Aberration: A Case Report. Am J Kidney Dis. 2022 May;79(5):760-764. doi: 10.1053/j.ajkd.2021.07.012. Epub 2021 Aug 27.
- Portuguese AJ, Gauthier J, Tykodi SS, Hall ET, Hirayama AV, Yeung CCS, Blosser CD. CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review. Bone Marrow Transplant. 2023 Apr;58(4):353-359. doi: 10.1038/s41409-022-01907-z. Epub 2022 Dec 27.
- Guzzo I, Becilli M, Cappoli A, Merli P, Labbadia R, Del Bufalo F, Tomas NM, Colucci M, Huber TB, Algeri M, Andreani M, Emma F, Locatelli F. Anti-CD19 chimeric antigen receptor T-cell therapy in a highly sensitized patient with focal and segmental glomerulosclerosis. Pediatr Nephrol. 2025 Nov;40(11):3513-3519. doi: 10.1007/s00467-025-06884-1. Epub 2025 Jul 16.
- Wang F, He K, Wang J, Zhao MH, Li Y, Zhang L, Saran R, Bragg-Gresham JL. Prevalence and Risk Factors for CKD: A Comparison Between the Adult Populations in China and the United States. Kidney Int Rep. 2018 Jun 2;3(5):1135-1143. doi: 10.1016/j.ekir.2018.05.011. eCollection 2018 Sep.
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- WestChina-BITE-cAMR
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