CD38 mAb Induction + Azathioprine Maintenance for Chronic Active AMR in Kidney Transplant Recipients | NCT07718308

NCT07718308

Overview

NCT ID: NCT07718308
Lead Sponsor: wujianyongOTHER
Official Title: 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
Brief Summary: 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.

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Jul 21, 2026Actual
Start Date: Jul 15, 2026Estimated
Primary Completion Date: Mar 15, 2028Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: 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.

Study Plan

Study Type: Interventional
Phase: Not Applicable
Enrollment: 20Estimated
Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

Contacts and Locations

Central Contacts: Chunchun Wei, MDContact
327530957@qq.com+8613738053172

Similar Studies

Participant Group/Arms

Experimental: CD38 mAb Induction + Azathioprine Sequential MaintenanceExperimental

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).

Biological: CD38

Drug: Azathioprine (AZA)

Other: Standard Triple Immunosuppression Maintenance