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CD38 mAb Induction + Azathioprine Maintenance for Chronic Active AMR in Kidney Transplant Recipients (CAZA)

2026년 7월 16일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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).

연구 유형

중재적

등록 (추정된)

20

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Chunchun Wei, MD
  • 전화번호: +8613738053172
  • 이메일: 327530957@qq.com

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  1. Voluntary written informed consent.
  2. Age ≥18 years.
  3. Kidney transplant (living or deceased donor) ≥180 days prior.
  4. eGFR ≥30 mL/min/1.73 m² (CKD-EPI 2021).
  5. Currently on stable triple immunosuppression (CNI + MMF + steroid) for ≥4 weeks, no severe related adverse effects.
  6. Positive HLA Class I and/or Class II donor-specific antibodies (DSA).
  7. Transplant kidney biopsy meeting Banff 2022 criteria for chronic active antibody-mediated rejection (caABMR).
  8. TPMT/NUDT15 genotyping: non-homozygous mutant (normal or intermediate metabolizer).

Exclusion Criteria:

  1. Participating in another clinical trial.
  2. Age <18 years.
  3. Pregnant, breastfeeding, or inadequate contraception in females.
  4. ABO-incompatible transplant.
  5. TPMT/NUDT15 homozygous mutant genotype.
  6. Biopsy shows any of: T-cell mediated rejection (TCMR), new/recurrent severe thrombotic microangiopathy, or polyomavirus nephropathy.
  7. Received anti-rejection therapy in prior 3 months.
  8. Received other immunomodulatory monoclonal/polyclonal antibodies (anti-CD20, bortezomib, anti-C5, anti-IL-6/IL-6R) in prior 3 months.
  9. Total bilirubin >2×ULN or ALT/AST >2.5×ULN.
  10. Hemoglobin <8 g/dL.
  11. Platelets <100×10^9/L.
  12. WBC <3×10^9/L or neutrophils <1.5×10^9/L.
  13. Hypogammaglobulinemia: IgG <400 mg/dL.
  14. Active bacterial, viral, or fungal infection.
  15. Active malignancy requiring intensified immunosuppression.
  16. Latent or active tuberculosis.
  17. Live vaccine within 6 weeks of screening.
  18. History of alcohol or illicit drug abuse.
  19. Severe medical or psychiatric illness likely to impair study participation.
  20. Active hepatitis B.
  21. Known hypersensitivity to CD38 mAb, azathioprine, or study drug components, or severe drug allergy history.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance

All enrolled caABMR patients receive:

  • Single subcutaneous injection of CD38 monoclonal antibody 1800 mg at baseline (Day 0).
  • Immediate conversion from mycophenolate mofetil to azathioprine (AZA), dosed according to TPMT/NUDT15 genotype and adjusted to achieve NK cell count <20/μL.
  • Continued standard triple immunosuppression: corticosteroid + azathioprine + tacrolimus (trough 5-7 ng/mL) or cyclosporine (trough 150-250 ng/mL).
  • Protocol-driven monitoring and 28-week surveillance biopsy. No control arm (single-arm exploratory design justified by lack of approved therapy and emerging evidence for CD38 targeting in AMR).
생물학적: CD38
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).
다른 이름들:
  • CD38 mAb
  • anti-CD38 monoclonal antibody
의약품: Azathioprine (AZA)
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.
다른 이름들:
  • 아자
  • Imuran (or generic)
다른: Standard Triple Immunosuppression Maintenance
Continued per local practice with protocol targets

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Slope of estimated glomerular filtration rate (eGFR) decline
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Change in peripheral blood NK cell, T cell and B cell subset counts and percentages measured by flow cytometry
기간: 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
기간: 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)
기간: 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)
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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

기타 결과 측정

결과 측정
측정값 설명
기간
Outcome Measure Title：Incidence of injection-related adverse reactions
기간: 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)
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

wujianyong

수사관

  • 수석 연구원: Jianyong Wu, MD, Zhejiang University

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 15일

기본 완료 (추정된)

2028년 3월 15일

연구 완료 (추정된)

2028년 3월 15일

연구 등록 날짜

최초 제출

2026년 7월 11일

QC 기준을 충족하는 최초 제출

2026년 7월 16일

처음 게시됨 (실제)

2026년 7월 21일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 21일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 16일

마지막으로 확인됨

2026년 7월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • IIT20260074C-R1

개별 참가자 데이터(IPD) 계획

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아니요

약물 및 장치 정보, 연구 문서

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아니

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아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

신장 이식에 대한 임상 시험

CD38에 대한 임상 시험

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스폰서 및 공동 작업자

건강 상태

약물 개입

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정황

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약물 개입

식이 보충제

스폰서 / 협력자

위치

구독하다