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

ConditionsKidney Transplantation Antibody-mediated Rejection

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

Sponsorwujianyong

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

Participating in another clinical trial.

Age <18 years.

Pregnant, breastfeeding, or inadequate contraception in females.

ABO-incompatible transplant.

Trial design

Design model

Single group

Treatments tested in this trial

CD38
Biological/Vaccine
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).
Azathioprine (AZA)
Drug
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.
Standard Triple Immunosuppression Maintenance
Other intervention
Continued per local practice with protocol targets

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: Experimental: CD38 mAb Induction + Azathioprine Sequential MaintenanceExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

Slope of estimated glomerular filtration rate (eGFR) decline

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.

Time frame

Baseline through Week 28, planned assessments at weeks 0, 4, 8, 12, 16, 20, 24, 28

Secondary outcomes

Change in peripheral blood NK cell, T cell and B cell subset counts and percentages measured by flow cytometry

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.

Time frame

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

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.

Time frame

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)

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.

Time frame

Baseline and Week 28

Relative percentage change in donor-specific antibody (DSA) mean fluorescence intensity (MFI)

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.

Time frame

Baseline, Week 8, Week 28

Other outcomes

Outcome Measure Title：Incidence of injection-related adverse reactions

All infusion-related adverse events during the whole follow-up period will be recorded, including fever, chills, hypotension, dyspnea and other infusion-associated manifestations.

Time frame

Through Week 28

Incidence of adverse events (AE) and serious adverse events (SAE)

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.

Time frame

Through Week 28

Incidence of liver function abnormalities

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.

Time frame

Through Week 28

Incidence of all-cause hospitalization

All hospitalization events for any reason during follow-up will be documented, including the admission time, diagnosis and length of hospital stay.

Time frame

Through Week 28

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

wujianyong

Lead sponsor

First Affiliated Hospital of Zhejiang University

Sponsor institution

Source ClinicalTrials.gov

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