Kidney TransplantationCAZANCT07718308
CD38 mAb Induction + Azathioprine Maintenance for Chronic Active AMR in Kidney Transplant Recipients
A study testing CD38, Azathioprine (AZA) and Standard Triple Immunosuppression Maintenance in people with Kidney Transplantation and Antibody-mediated Rejection, run by wujianyong.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation, Antibody-mediated Rejection
- What is being tested?
- CD38, Azathioprine (AZA) and Standard Triple Immunosuppression Maintenance
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2026to 15 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
Read the detailed description
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).
- Being tested
- CD38, Azathioprine (AZA), Standard Triple Immunosuppression Maintenance
- Keywords
- Daratumumab, Banff 2022 classification, Azathioprine, Natural killer cell, Donor specific antibody, eGFR slope, Chronic active AMR, CD38 antibody, Sequential immunosuppression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD38Biological
Also called CD38 mAb, anti-CD38 monoclonal antibody
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
Also called AZA, Imuran (or generic)
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 MaintenanceOther
Continued per local practice with protocol targets
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Biological: CD38; Drug: Azathioprine (AZA); Other: Standard Triple Immunosuppression Maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 8, Week 28
Change in Transplant Kidney Biopsy Pathology Scores (Banff 2022)
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.
Measured: Baseline, Week 28
Incidence of Acute Rejection (TCMR, AMR, or Mixed)
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.
Measured: Through Week 28
Patient overall survival rate
The proportion of subjects who remain alive without all-cause mortality at the designated follow-up time point
Measured: Week 28
Graft survival rate
Percentage of participants with functioning renal allograft, defined as no return to maintenance dialysis and no secondary kidney retransplantation
Measured: Week 28
Incidence of BK Virus (BKV) Infection
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.
Measured: Through Week 28
Incidence of Cytomegalovirus (CMV) Infection
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.
Measured: Through Week 28
Incidence of Neutropenia
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.
Measured: Through Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2026
- Study start15 Jul 2026 (estimated)
- Primary completion15 Mar 2028 (estimated)
- Study completion15 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- wujianyong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, wujianyong, First Affiliated Hospital of Zhejiang University
- Investigators
- Jianyong Wu, MD, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07718308
- Sponsor's protocol ID
- IIT20260074C-R1
- Acronym
- CAZA
- Status last verified
- Jul 2026
- First submitted
- 11 Jul 2026
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
ten Berge RJ, Schellekens PT, Surachno S, The TH, ten Veen JH, Wilmink JM. A longitudinal study on the effects of azathioprine and high doses of prednisone on the immune system of kidney-transplant recipients. Clin Immunol Immunopathol. 1982 Jul;24(1):33-46. doi: 10.1016/0090-1229(82)90086-1. No abstract available.
PubMed 7049473Hoffmann U, Neudorfl C, Daemen K, Keil J, Stevanovic-Meyer M, Lehner F, Haller H, Blume C, Falk CS. NK Cells of Kidney Transplant Recipients Display an Activated Phenotype that Is Influenced by Immunosuppression and Pathological Staging. PLoS One. 2015 Jul 6;10(7):e0132484. doi: 10.1371/journal.pone.0132484. eCollection 2015.
PubMed 26147651Prince HE, Ettenger RB, Dorey FJ, Fine RN, Fahey JL. Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients. Transplant Proc. 1984 Dec;16(6):1475-7. No abstract available.
PubMed 6390849Reinders ME, Hoogduijn MJ. NK Cells and MSCs: Possible Implications for MSC Therapy in Renal Transplantation. J Stem Cell Res Ther. 2014 Feb 7;4(2):1000166. doi: 10.4172/2157-7633.1000166. No abstract available.
PubMed 24900946Chambon M, Koenig A. NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection. Transpl Int. 2024 Oct 16;37:13318. doi: 10.3389/ti.2024.13318. eCollection 2024.
PubMed 39479216Chocair PR, Neves PDMM, Mohrbacher S, Neto MP, Sato VAH, Oliveira ES, Barbosa LV, Bales AM, da Silva FP, Cuvello-Neto AL, Duley JA. Case Report: Azathioprine: An Old and Wronged Immunosuppressant. Front Immunol. 2022 Jun 10;13:903012. doi: 10.3389/fimmu.2022.903012. eCollection 2022.
PubMed 35757730Bohmig GA, Naesens M, Viklicky O, Thaunat O, Diebold M, Rostaing L, Budde K. Antibody-mediated rejection-treatment standard. Nephrol Dial Transplant. 2025 Aug 1;40(8):1615-1627. doi: 10.1093/ndt/gfaf097.
PubMed 40440205Matignon M, Grimbert P, Moktefi A, Pilon C. Anti-CD38 and Regression of Chronic Active Antibody-Mediated Rejection After Kidney Transplantation - Myth or Reality? Kidney Int Rep. 2025 Sep 2;10(10):3305-3307. doi: 10.1016/j.ekir.2025.08.031. eCollection 2025 Oct. No abstract available.
PubMed 41141512Mayer KA, Budde K, Diebold M, Halloran PF, Bohmig GA. Targeting CD38 in Antibody-Mediated Rejection. Transpl Int. 2025 May 15;38:14343. doi: 10.3389/ti.2025.14343. eCollection 2025.
PubMed 40444214Etieve R, Van Wynsberghe M, Grange S, Laurent C, Lemoine M, Candon S, Bertrand D, de Nattes T. One tool, multiple gains: anti-CD38 therapy in antibody-mediated rejection. Clin Kidney J. 2025 Sep 11;18(Suppl 2):ii55-ii64. doi: 10.1093/ckj/sfaf283. eCollection 2025 Dec.
PubMed 41393858Mayer KA, Schrezenmeier E, Diebold M, Halloran PF, Schatzl M, Schranz S, Haindl S, Kasbohm S, Kainz A, Eskandary F, Doberer K, Patel UD, Dudani JS, Regele H, Kozakowski N, Klager J, Boxhammer R, Amann K, Puchhammer-Stockl E, Vietzen H, Beck J, Schutz E, Akifova A, Firbas C, Gilbert HN, Osmanodja B, Halleck F, Jilma B, Budde K, Bohmig GA. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med. 2024 Jul 11;391(2):122-132. doi: 10.1056/NEJMoa2400763. Epub 2024 May 25.
PubMed 38804514Kwun J, Matignon M, Manook M, Guendouz S, Audard V, Kheav D, Poullot E, Gautreau C, Ezekian B, Bodez D, Damy T, Faivre L, Menouche D, Yoon J, Park J, Belhadj K, Chen D, Bilewski AM, Yi JS, Collins B, Stegall M, Farris AB, Knechtle S, Grimbert P. Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use. J Am Soc Nephrol. 2019 Jul;30(7):1206-1219. doi: 10.1681/ASN.2018121254. Epub 2019 Jun 21.
PubMed 31227636Yang D, Agrawal N, Marcus C, Roy N, Richards KR, Nahas MR, Cardarelli F. Treatment of Multiple Myeloma With Daratumumab in a Kidney Transplant Patient. Am J Ther. 2021 Jul-Aug 01;28(4):e488-e491. doi: 10.1097/MJT.0000000000001024.
PubMed 34228654Lye WC, Loh HL. Anti-CD38 Daratumumab Treatment of Chronic Active Antibody-Mediated Kidney Allograft Rejection. Kidney Int Rep. 2025 Jul 15;10(10):3506-3515. doi: 10.1016/j.ekir.2025.07.009. eCollection 2025 Oct.
PubMed 41141546Milani P, Basset M, Curci P, Foli A, Rizzi R, Nuvolone M, Guido R, Gesualdo L, Specchia G, Merlini G, Palladini G. Daratumumab in light chain deposition disease: rapid and profound hematologic response preserves kidney function. Blood Adv. 2020 Apr 14;4(7):1321-1324. doi: 10.1182/bloodadvances.2020001553.
PubMed 32251496
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07718308
- Acronym / sponsor ID
- CAZA / IIT20260074C-R1
- Keywords
- Daratumumab, Banff 2022 classification, Azathioprine, Natural killer cell, Donor specific antibody, eGFR slope, Chronic active AMR, CD38 antibody
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- wujianyongUniversity, hospital or other
- Study start
- 15 Jul 2026 (estimated)
- Primary completion
- 15 Mar 2028 (estimated)
- Study completion
- 15 Mar 2028 (estimated)
- First posted
- 21 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance | Experimental | Biological: CD38, Drug: Azathioprine (AZA), Other: Standard Triple Immunosuppression MaintenanceAll 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- Participating in another clinical trial.
- Age <18 years.
- Pregnant, breastfeeding, or inadequate contraception in females.
- ABO-incompatible transplant.
- TPMT/NUDT15 homozygous mutant genotype.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD38Also: CD38 mAb, anti-CD38 monoclonal antibodySingle 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). | Biological | Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance |
| Azathioprine (AZA)Also: AZA, Imuran (or generic)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. | Drug | Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance |
| Standard Triple Immunosuppression MaintenanceContinued per local practice with protocol targets | Other | Experimental: CD38 mAb Induction + Azathioprine Sequential Maintenance |
Primary outcome
Slope of estimated glomerular filtration rate (eGFR) decline
Time frame: 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.
11 secondary outcomes
Change in peripheral blood NK cell, T cell and B cell subset counts and percentages measured by flow cytometry
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
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)
Time frame: Baseline and Week 28
Relative percentage change in donor-specific antibody (DSA) mean fluorescence intensity (MFI)
Time frame: Baseline, Week 8, Week 28
Change in Transplant Kidney Biopsy Pathology Scores (Banff 2022)
Time frame: Baseline, Week 28
Incidence of Acute Rejection (TCMR, AMR, or Mixed)
Time frame: Through Week 28
Patient overall survival rate
Time frame: Week 28
Graft survival rate
Time frame: Week 28
Incidence of BK Virus (BKV) Infection
Time frame: Through Week 28
Incidence of Cytomegalovirus (CMV) Infection
Time frame: Through Week 28
Incidence of Neutropenia
Time frame: Through Week 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Results publication: PubMed 7049473ten Berge RJ, Schellekens PT, Surachno S, The TH, ten Veen JH, Wilmink JM. A longitudinal study on the effects of azathioprine and high doses of prednisone on the immune system of kidney-transplant recipients. Clin Immunol Immunopathol. 1982 Jul;24(1):33-46. doi: 10.1016/0090-1229(82)90086-1. No abstract available.
- Results publication: PubMed 26147651Hoffmann U, Neudorfl C, Daemen K, Keil J, Stevanovic-Meyer M, Lehner F, Haller H, Blume C, Falk CS. NK Cells of Kidney Transplant Recipients Display an Activated Phenotype that Is Influenced by Immunosuppression and Pathological Staging. PLoS One. 2015 Jul 6;10(7):e0132484. doi: 10.1371/journal.pone.0132484. eCollection 2015.
- Results publication: PubMed 6390849Prince HE, Ettenger RB, Dorey FJ, Fine RN, Fahey JL. Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients. Transplant Proc. 1984 Dec;16(6):1475-7. No abstract available.
- Results publication: PubMed 24900946Reinders ME, Hoogduijn MJ. NK Cells and MSCs: Possible Implications for MSC Therapy in Renal Transplantation. J Stem Cell Res Ther. 2014 Feb 7;4(2):1000166. doi: 10.4172/2157-7633.1000166. No abstract available.
- Results publication: PubMed 39479216Chambon M, Koenig A. NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection. Transpl Int. 2024 Oct 16;37:13318. doi: 10.3389/ti.2024.13318. eCollection 2024.
- Results publication: PubMed 35757730Chocair PR, Neves PDMM, Mohrbacher S, Neto MP, Sato VAH, Oliveira ES, Barbosa LV, Bales AM, da Silva FP, Cuvello-Neto AL, Duley JA. Case Report: Azathioprine: An Old and Wronged Immunosuppressant. Front Immunol. 2022 Jun 10;13:903012. doi: 10.3389/fimmu.2022.903012. eCollection 2022.
- Results publication: PubMed 40440205Bohmig GA, Naesens M, Viklicky O, Thaunat O, Diebold M, Rostaing L, Budde K. Antibody-mediated rejection-treatment standard. Nephrol Dial Transplant. 2025 Aug 1;40(8):1615-1627. doi: 10.1093/ndt/gfaf097.
- Results publication: PubMed 41141512Matignon M, Grimbert P, Moktefi A, Pilon C. Anti-CD38 and Regression of Chronic Active Antibody-Mediated Rejection After Kidney Transplantation - Myth or Reality? Kidney Int Rep. 2025 Sep 2;10(10):3305-3307. doi: 10.1016/j.ekir.2025.08.031. eCollection 2025 Oct. No abstract available.
- Results publication: PubMed 40444214Mayer KA, Budde K, Diebold M, Halloran PF, Bohmig GA. Targeting CD38 in Antibody-Mediated Rejection. Transpl Int. 2025 May 15;38:14343. doi: 10.3389/ti.2025.14343. eCollection 2025.
- Results publication: PubMed 41393858Etieve R, Van Wynsberghe M, Grange S, Laurent C, Lemoine M, Candon S, Bertrand D, de Nattes T. One tool, multiple gains: anti-CD38 therapy in antibody-mediated rejection. Clin Kidney J. 2025 Sep 11;18(Suppl 2):ii55-ii64. doi: 10.1093/ckj/sfaf283. eCollection 2025 Dec.
- Results publication: PubMed 38804514Mayer KA, Schrezenmeier E, Diebold M, Halloran PF, Schatzl M, Schranz S, Haindl S, Kasbohm S, Kainz A, Eskandary F, Doberer K, Patel UD, Dudani JS, Regele H, Kozakowski N, Klager J, Boxhammer R, Amann K, Puchhammer-Stockl E, Vietzen H, Beck J, Schutz E, Akifova A, Firbas C, Gilbert HN, Osmanodja B, Halleck F, Jilma B, Budde K, Bohmig GA. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med. 2024 Jul 11;391(2):122-132. doi: 10.1056/NEJMoa2400763. Epub 2024 May 25.
- Results publication: PubMed 31227636Kwun J, Matignon M, Manook M, Guendouz S, Audard V, Kheav D, Poullot E, Gautreau C, Ezekian B, Bodez D, Damy T, Faivre L, Menouche D, Yoon J, Park J, Belhadj K, Chen D, Bilewski AM, Yi JS, Collins B, Stegall M, Farris AB, Knechtle S, Grimbert P. Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use. J Am Soc Nephrol. 2019 Jul;30(7):1206-1219. doi: 10.1681/ASN.2018121254. Epub 2019 Jun 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jianyong Wu, MD principal investigator
First Affiliated Hospital of Zhejiang University
Questions about this trial
What is this clinical trial studying?
A study testing CD38, Azathioprine (AZA) and Standard Triple Immunosuppression Maintenance in people with Kidney Transplantation and Antibody-mediated Rejection, run by wujianyong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chunchun Wei, MD (+8613738053172, 327530957@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slope of estimated glomerular filtration rate (eGFR) decline (time frame: Baseline through Week 28, planned assessments at weeks 0, 4, 8, 12, 16, 20, 24, 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07718308, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.