CD38 mAb Induction + Azathioprine Maintenance for Chronic Active AMR in Kidney Transplant Recipients (CAZA)
2026年7月16日 更新者：wujianyong
A Multicenter Exploratory Clinical Study of Targeted NK Cell Inhibition for Transplant Kidney Chronic Active Antibody-Mediated Rejection (caABMR): Single Induction With CD38 Monoclonal Antibody Followed by Sequential Maintenance With Azathioprine
This multicenter, prospective, single-arm exploratory study evaluates the efficacy and safety of a novel sequential regimen for chronic active antibody-mediated rejection (caABMR) in kidney transplant recipients: single-dose CD38 monoclonal antibody (1800 mg subcutaneous) induction to deplete plasma cells and NK cells, followed by long-term maintenance with azathioprine (replacing mycophenolate mofetil) plus standard triple immunosuppression (steroid + calcineurin inhibitor).
The regimen aims to control DSA-driven injury, stabilize or improve graft function (primary: eGFR decline slope), reduce DSA, improve pathology (Banff 2022), and minimize infection/nephrotoxicity risks associated with intensified or prolonged biologic therapy.
Twenty patients across 6 Chinese transplant centers will be enrolled.
CD38 mAb, azathioprine, key monitoring tests (HLA antibody, pharmacogenomics, immune profiling) are provided free by the study team (~40,000 RMB per patient).
Ethics approved; informed consent obtained.
研究概览
地位
尚未招聘
详细说明
Background: caABMR is the leading cause of late kidney allograft loss. Current therapies (plasmapheresis, IVIG, rituximab, bortezomib, long-term CD38 mAb) have limited efficacy, high recurrence, significant side effects, and high cost with no approved standard.
Rationale: CD38 mAb depletes antibody-producing plasma cells and pathogenic NK cells, rapidly lowering DSA and micro vascular inflammation. However, long-term monotherapy is costly and may increase infection risk. This study uses single induction dose + switch to azathioprine (safe, inexpensive, long-used in transplantation, suppresses NK activity) for durable, affordable maintenance. TPMT/NUDT15 genotyping guides personalized AZA dosing; serial NK cell monitoring targets <20/μL.
Design: Multicenter (6 centers), prospective, open-label, single-arm, exploratory (N=20).
Intervention: Baseline: CD38 mAb 1800 mg SC x1 + immediate switch MMF→AZA (dose per genotype: normal metabolizer 2-3 mg/kg/d; intermediate 0.6-2.4 mg/kg/d). Maintain triple IS (steroid + AZA + Tac target 5-7 ng/mL or CsA 150-250 ng/mL).
研究类型
介入性
注册 (估计的)
20
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Chunchun Wei, MD
- 电话号码：+8613738053172
- 邮箱：327530957@qq.com
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- Voluntary written informed consent.
- Age ≥18 years.
- Kidney transplant (living or deceased donor) ≥180 days prior.
- eGFR ≥30 mL/min/1.73 m² (CKD-EPI 2021).
- Currently on stable triple immunosuppression (CNI + MMF + steroid) for ≥4 weeks, no severe related adverse effects.
- Positive HLA Class I and/or Class II donor-specific antibodies (DSA).
- Transplant kidney biopsy meeting Banff 2022 criteria for chronic active antibody-mediated rejection (caABMR).
- TPMT/NUDT15 genotyping: non-homozygous mutant (normal or intermediate metabolizer).
Exclusion Criteria:
- Participating in another clinical trial.
- Age <18 years.
- Pregnant, breastfeeding, or inadequate contraception in females.
- ABO-incompatible transplant.
- TPMT/NUDT15 homozygous mutant genotype.
- Biopsy shows any of: T-cell mediated rejection (TCMR), new/recurrent severe thrombotic microangiopathy, or polyomavirus nephropathy.
- Received anti-rejection therapy in prior 3 months.
- Received other immunomodulatory monoclonal/polyclonal antibodies (anti-CD20, bortezomib, anti-C5, anti-IL-6/IL-6R) in prior 3 months.
- Total bilirubin >2×ULN or ALT/AST >2.5×ULN.
- Hemoglobin <8 g/dL.
- Platelets <100×10^9/L.
- WBC <3×10^9/L or neutrophils <1.5×10^9/L.
- Hypogammaglobulinemia: IgG <400 mg/dL.
- Active bacterial, viral, or fungal infection.
- Active malignancy requiring intensified immunosuppression.
- Latent or active tuberculosis.
- Live vaccine within 6 weeks of screening.
- History of alcohol or illicit drug abuse.
- Severe medical or psychiatric illness likely to impair study participation.
- Active hepatitis B.
- Known hypersensitivity to CD38 mAb, azathioprine, or study drug components, or severe drug allergy history.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance
All enrolled caABMR patients receive:
|
Single 1800 mg subcutaneous injection at baseline to induce rapid depletion of plasma cells (source of DSA) and NK cells (key effectors of microvascular injury in caABMR).
Marketed anti-CD38 mAb (off-label use in this indication).
其他名称：
Oral azathioprine maintenance (replaces mycophenolate), individualized starting dose 2.0-3.0 mg/kg/day (normal TPMT/NUDT15 metabolizer) or 30-80% reduced (intermediate metabolizer), titrated per serial NK cell counts and hematologic tolerance.
Long-term NK suppression to maintain immune balance and protect graft.
其他名称：
Continued per local practice with protocol targets
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Slope of estimated glomerular filtration rate (eGFR) decline
大体时间：Baseline through Week 28, planned assessments at weeks 0, 4, 8, 12, 16, 20, 24, 28
|
The primary efficacy endpoint is the slope of eGFR decline over 28 weeks, calculated from serial serum creatinine measurements (every 4 weeks) using the 2021 CKD-EPI equation.
Serum creatinine is measured by enzymatic method or isotope dilution mass spectrometry.
Slope is estimated via linear mixed-effects model or ordinary least-squares regression per patient, then summarized.
Negative slope indicates ongoing graft loss; less negative or positive slope indicates stabilization or improvement of renal function after treatment.
|
Baseline through Week 28, planned assessments at weeks 0, 4, 8, 12, 16, 20, 24, 28
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in peripheral blood NK cell, T cell and B cell subset counts and percentages measured by flow cytometry
大体时间：Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
|
Quantitative detection of lymphocyte subpopulations (NK, T, B cells) in peripheral blood via flow cytometry; evaluate the absolute count and relative percentage changes at each follow-up time point.
|
Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
|
|
Absolute and relative percentage change in estimated glomerular filtration rate calculated by CKD-EPI 2021 formula
大体时间：Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
|
Estimated glomerular filtration rate (eGFR) is calculated by the CKD-EPI 2021 formula.
Both absolute value and relative percentage change of eGFR will be evaluated at all scheduled follow-up visits.
|
Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28
|
|
Percentage change in urine protein-to-creatinine ratio (UPCR)
大体时间：Baseline and Week 28
|
Urine protein-to-creatinine ratio (UPCR) measured in mg/g or mg/mmol.
Urine protein is tested via pyrogallol red molybdate method, and creatinine is detected using sarcosine oxidase assay.
The relative percentage change of UPCR is used to evaluate renal therapeutic efficacy.
|
Baseline and Week 28
|
|
Relative percentage change in donor-specific antibody (DSA) mean fluorescence intensity (MFI)
大体时间：Baseline, Week 8, Week 28
|
Donor-specific antibody MFI is detected via Luminex single-antigen bead assay.
Relative percentage change from baseline will be calculated to evaluate the reduction of alloantibody levels.
|
Baseline, Week 8, Week 28
|
|
Change in Transplant Kidney Biopsy Pathology Scores (Banff 2022)
大体时间：Baseline, Week 28
|
Banff 2022 renal allograft pathology scoring system is applied for the interpretation of protocol kidney biopsy specimens.
The scores include microcirculation inflammation, tubulitis, interstitial inflammation, chronic glomerulopathy, transplant glomerulitis and chronic arteriopathy.
The pathological scores are recorded at screening baseline and week-28 follow-up biopsy.
The variation of each individual Banff lesion score between two time-points will be analyzed.
Higher Banff lesion scores represent more severe renal allograft injury.
|
Baseline, Week 28
|
|
Incidence of Acute Rejection (TCMR, AMR, or Mixed)
大体时间：Through Week 28
|
Cumulative incidence (%) of biopsy-proven acute rejection, including T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and mixed rejection, diagnosed according to Banff 2022 classification criteria.
|
Through Week 28
|
|
Patient overall survival rate
大体时间：Week 28
|
The proportion of subjects who remain alive without all-cause mortality at the designated follow-up time point
|
Week 28
|
|
Graft survival rate
大体时间：Week 28
|
Percentage of participants with functioning renal allograft, defined as no return to maintenance dialysis and no secondary kidney retransplantation
|
Week 28
|
|
Incidence of BK Virus (BKV) Infection
大体时间：Through Week 28
|
Cases of BK virus infection are categorized as BKV viruria (>10³ copies/mL), BKV viremia (≥10⁴ copies/mL), or biopsy-confirmed BKV nephropathy identified by renal histology combined with SV40 IHC or ISH staining.
Cumulative incidence percentage will be calculated for each category.
|
Through Week 28
|
|
Incidence of Cytomegalovirus (CMV) Infection
大体时间：Through Week 28
|
Cytomegalovirus infection is defined as detectable CMV DNA ≥10³ copies/mL quantified via quantitative PCR (qPCR).
Cumulative incidence percentage of affected subjects will be summarized.
|
Through Week 28
|
|
Incidence of Neutropenia
大体时间：Through Week 28
|
Neutropenia is stratified by absolute neutrophil count (ANC): mild ANC <1.5×10⁹/L, moderate ANC <1.0×10⁹/L, severe ANC <0.5×10⁹/L.
Cumulative incidence percentage will be stratified by severity grades defined per NCI CTCAE or study protocol criteria.
|
Through Week 28
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Outcome Measure Title：Incidence of injection-related adverse reactions
大体时间：Through Week 28
|
All infusion-related adverse events during the whole follow-up period will be recorded, including fever, chills, hypotension, dyspnea and other infusion-associated manifestations.
|
Through Week 28
|
|
Incidence of adverse events (AE) and serious adverse events (SAE)
大体时间：Through Week 28
|
The type, severity, relation to study medication and occurrence frequency of all adverse events and serious adverse events will be collected, according to CTCAE common terminology criteria.
|
Through Week 28
|
|
Incidence of liver function abnormalities
大体时间：Through Week 28
|
Liver function indexes including alanine transaminase, aspartate transaminase, total bilirubin will be tested regularly.
Liver function abnormality is defined as laboratory elevation exceeding 3-fold upper limit of normal range.
|
Through Week 28
|
|
Incidence of all-cause hospitalization
大体时间：Through Week 28
|
All hospitalization events for any reason during follow-up will be documented, including the admission time, diagnosis and length of hospital stay.
|
Through Week 28
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
调查人员
- 首席研究员：Jianyong Wu, MD、Zhejiang University
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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- Caliskan Y, Mirioglu S, Dirim AB, Ozluk Y, Yegit O, Aksoy E, Safak S, Guller N, Demir E, Artan AS, Oto OA, Besisik S, Yazici H, Turkmen A, Lentine KL. A comparison of methods of plasmapheresis for the treatment of late antibody mediated rejection in kidney transplant recipients. Ther Apher Dial. 2023 Jun;27(3):428-434. doi: 10.1111/1744-9987.13937. Epub 2022 Oct 14.
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研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年7月15日
初级完成 (估计的)
2028年3月15日
研究完成 (估计的)
2028年3月15日
研究注册日期
首次提交
2026年7月11日
首先提交符合 QC 标准的
2026年7月16日
首次发布 (实际的)
2026年7月21日
研究记录更新
最后更新发布 (实际的)
2026年7月21日
上次提交的符合 QC 标准的更新
2026年7月16日
最后验证
2026年7月1日
更多信息
与本研究相关的术语
关键字
其他研究编号
- IIT20260074C-R1
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
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研究美国 FDA 监管的设备产品
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此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.