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

NCT07718308 | Not Yet Recruiting

• 1 other identifier: IIT20260074C-R1
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Kidney Transplantation; Antibody-mediated Rejection

Keywords

Daratumumab; Banff 2022 classification; Azathioprine; Natural killer cell; Donor specific antibody; eGFR slope; Chronic active AMR; CD38 antibody; Sequential immunosuppression

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (11)

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

  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

  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)

  Baseline and Week 28

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

  Baseline, Week 8, Week 28

• Change in Transplant Kidney Biopsy Pathology Scores (Banff 2022)

  Baseline, Week 28

Other Outcomes (4)

• Outcome Measure Title：Incidence of injection-related adverse reactions

  Through Week 28

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

  Through Week 28

• Incidence of liver function abnormalities

  Through Week 28

Study Arms (1)

Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance

EXPERIMENTAL

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

Interventions

CD38 BIOLOGICAL

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).

Also known as: CD38 mAb, anti-CD38 monoclonal antibody

Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance

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.

Also known as: AZA, Imuran (or generic)

Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance

Standard Triple Immunosuppression Maintenance OTHER

Continued per local practice with protocol targets

Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• wujianyong: lead

Related Publications (25)

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MeSH Terms

Interventions

daratumumab; Azathioprine

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jianyong Wu, MD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunchun Wei, MD

CONTACT

+8613738053172; 327530957@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Nephrology Center / Chief Physician

Study Record Dates

• First Submitted: July 11, 2026
• First Posted: July 21, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 15, 2028
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share