Safety and Efficacy of the Bispecific T-Cell Engager (BiTE) in Kidney Transplant Recipients With Chronic Active Antibody-Mediated Rejection

Обзор

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).

Вмешательства

• Препарат BiTE (BCMA x CD3 Bispecific Antibody)
  Subcutaneous administration of BCMA x CD3 Bispecific Antibody

Первичные конечные точки

• Incidence of treatment-emergent adverse events [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (11)

• Leukocyte subsets in peripheral blood [Срок оценки: Through study completion, an average of 1 year]
• Serum immunoglobulin levels [Срок оценки: Through study completion, an average of 1 year]
• Serum renal function [Срок оценки: Through study completion, an average of 1 year]
• HLA antibody detection [Срок оценки: Through study completion, an average of 1 year]
• Plasma donor-derived cell-free DNA [Срок оценки: Through study completion, an average of 1 year]
• Pathological analysis of renal allograft biopsy [Срок оценки: At baseline and every 6 months after treatment completion until study completion.]
• Ultrasound of the renal allograft [Срок оценки: Through study completion, an average of 1 year]
• Proteinuria: 24 hour urine protein [Срок оценки: Through study completion, an average of 1 year]
• Proteinuria: Urine protein to creatinine ratio [Срок оценки: Through study completion, an average of 1 year]
• Graft loss [Срок оценки: Through study completion, an average of 1 year]
• Death [Срок оценки: Through study completion, an average of 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital, Sichuan University — Чэнду

Публикации

• 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 PMID 32463180
• 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 i PMID 35661166
• 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 Sensitiz PMID 41692345
• 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. PMID 40722049
• 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 avail PMID 38096365
• 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. PMID 40534130
• 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-la PMID 34388396
• 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. PMID 39412823

Идентификаторы

NCT: NCT07689578 · WestChina-BITE-cAMR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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