A Phase 2 interventional study of Belimumab Prefilled Syringe [Benlysta] in Kidney Transplant Rejection, sponsored by Leiden University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Leiden University Medical Center · Phase 2, Interventional, and Diagnostic
The goal of this clinical trial is to determine whether belimumab can improve detection of circulating HLA-specific memory B cells to support safer and more effective donor organ allocation in highly sensitized kidney transplant candidates.
The main questions it aims to answer are:
Does treatment with belimumab change the antigen specificity profile of circulating HLA-specific memory B cells compared to pre-treatment measurements?
Does a delisting strategy that incorporates mobilized memory B cells improve the probability of donor organ allocation and reduce time to transplantation?
Participants will:
Receive a short course of belimumab treatment
Provide blood samples before and during treatment to assess memory B-cell profiles
Undergo evaluation for potential adjustment of unacceptable HLA specificities (delisting) based on test results
Be followed for donor organ allocation and transplantation outcomes
Kidney transplantation is the optimal treatment for patients with end-stage kidney disease, but access is limited by antibodies targeting non-self human leukocyte antigens (HLA). Antibody-mediated rejection (AMR) occurs when HLA molecules on the donor organ correspond to preformed antibodies in the transplant recipient, which may arise from sensitizing events such as prior organ transplantation, pregnancy, or blood transfusion. To prevent AMR, pre-transplant testing identifies the HLA specificities targeted by patient antibodies, and these specificities are listed as "unacceptable HLA specificities," thereby excluding donor kidneys with incompatible HLA molecules from allocation. Although registration of unacceptable HLA specificities reduces the probability of identifying a compatible donor, this strategy is generally accepted because it mitigates the risk of AMR. However, in highly sensitized transplant candidates, defined as those with HLA antibodies against ≥85% of the donor population, the probability of identifying a suitable donor becomes extremely low. Such patients often remain on transplant waiting lists for years and face a five-year mortality rate of approximately 50% associated with maintenance dialysis. Two approaches may subsequently be considered to improve allocation probability: delisting and desensitization.
Desensitization can be achieved using immunosuppressive agents targeting antibodies and antibody-producing cells. Current desensitization strategies are associated with a high risk of AMR and do not confer a survival benefit compared to remaining on the waiting list. Consequently, delisting should be considered as an initial strategy. Delisting enables transplantation despite the presence of preformed donor-specific antibodies (DSA) that confer a relatively low risk of AMR. Ideally, HLA specificities that occur frequently in the donor pool but pose minimal individual risk are selected for delisting.
Methods for defining low-risk HLA specificities remain imperfect, and no validated international delisting protocols are currently available. After exclusion of specificities associated with a positive complement-dependent cytotoxicity assay, clinicians frequently rely on semi-quantitative mean fluorescence intensity (MFI) values obtained from the Luminex single-antigen bead (SAB) assay. However, this assay is limited by non-standardized cut-off values, a weak correlation with HLA antibody titers, and a primary reflection of antibodies produced by plasma cells. Importantly, the assay does not account for memory B cells (mBC), which can rapidly regenerate antibody production after transplantation and contribute to "rebound" AMR. This limitation partially explains the variability in transplant outcomes associated with pre-transplant DSA exhibiting low MFI values. Direct assessment of HLA-specific mBC may therefore improve pre-transplant risk stratification.
A memory B-cell assay has been developed in which peripheral blood mononuclear cells (PBMCs) are polyclonally stimulated in vitro to identify HLA-specific antibodies produced by mBC. Antibodies detected in both PBMC supernatants and serum have been associated with an increased risk of AMR, whereas specificities detected only in serum may represent low-risk candidates for delisting. However, this assay may underestimate sensitization because most memory B cells reside in secondary lymphoid tissues and are not consistently present in the circulation.
Preclinical studies indicate that memory B-cell homing is dependent on the cytokine B-cell activating factor (BAFF). Belimumab, a monoclonal antibody targeting BAFF, disrupts this homing process and promotes mobilization of memory B cells into the bloodstream. Data from seven randomized trials in patients with Systemic lupus erythematosus demonstrate a median 2.2-fold increase in circulating mBC after four weeks of belimumab therapy, accompanied by reduced expression of genes related to activation and migration. In a prior analysis of seven highly sensitized kidney transplant candidates treated with four weekly belimumab injections, a broader HLA-specific mBC profile was observed, with additional identification of potential low-risk specificities (MFI 3,000-12,000) lacking mBC reactivity. These findings suggest a role for belimumab-enhanced profiling in delisting strategies.
The present clinical trial will evaluate whether a short, four-week course of belimumab enhances the detection of HLA antibodies produced by circulating HLA-specific mBC. The hypothesis is that improved detection will facilitate identification of low-risk specificities suitable for delisting, thereby expanding access to transplantation while limiting the risk of AMR. Secondary analyses will describe transplant outcomes following delisting and will assess the effects of belimumab on serum BAFF levels, B-cell and plasma-cell subsets, HLA antibody profiles, and memory B-cell transcriptomes.
Improved detection of clinically relevant memory B cells through a belimumab-enhanced assay may enable more accurate risk stratification and safer delisting decisions, thereby facilitating transplantation in highly sensitized candidates who would otherwise remain untransplanted.
Leiden University Medical Center is the lead sponsor of 334 studies on the registry; 110 are open to participants now.
Counted across the registry records on this site, refreshed daily.
To be eligible for participation in this study, a subject must meet all of the following criteria:
Adults aged ≥18 and ≤75 years Candidate for kidney transplantation
Highly sensitized, as determined by either:
Female subjects are eligible if they meet one of the following criteria:
Not pregnant or breastfeeding, as confirmed by a negative pregnancy test at screening Of non- (i.e., status post hysterectomy, , bilateral oophorectomy, documented bilateral tubal ligation, or other permanent sterilization procedure) Of childbearing potential and willing to use effective and agree not to become pregnant during the study
A potential subject who meets any of the following criteria will be excluded from participation:
Active pregnancy, as confirmed by a positive urine β-hCG test or a positive serum β-hCG test, adjusted for end-stage renal disease (ESRD) Significant hypogammaglobulinemia (IgG \<4.0 g/L) or IgA deficiency (IgA \<0.1 g/L) Receipt of any vaccination within 3 months prior to screening Enrollment in another clinical trial investigating an drug or device at the time of belimumab treatment and delisting; participation in a desensitization trial after assessment of the primary outcome is permitted
Previous administration of any of the following agents within 365 days prior to screening:
BAFF inhibitors (e.g., belimumab, tabalumab) Monoclonal antibodies targeting CD20 (e.g., rituximab) Monoclonal antibodies targeting CD52 (e.g., alemtuzumab) Lymphocyte-depleting agents (e.g., rATG, ATGAM) IL-6 inhibitors or IL-6/IL-6R modulators (e.g., tocilizumab, clazakizumab) Proteasome inhibitors (e.g., bortezomib) Previous administration of high-dose (>50 mg prednisolone or equivalent per day) within 90 days prior to screening
Active infection at screening, defined as any of the following:
Hospitalization for treatment within 30 days prior to screening Current use of parenteral (intravenous or intramuscular) antimicrobial therapy (including antibacterial, antiviral, antifungal, or antiparasitic agents) Current serologic evidence of viral hepatitis, defined as positivity for or HBcAb, or a positive antibody test without antiviral treatment Uncontrolled infection, defined as \<250 cells/mm³ and/or detectable viremia History of a primary immunodeficiency, including complement deficiencies \<1.5 × 10⁹/L Current indication for blood product transfusion at screening, or a high likelihood of requiring transfusion during the treatment phase, in the opinion of the investigator Significant history of infections that, in the opinion of the investigator, would make participation unsuitable History of anaphylactic or severe allergic reaction to parenteral administration of human or murine proteins or monoclonal antibodies Active or a history of malignancy within the past 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix with no evidence of disease for at least 3 years Evidence of psychiatric illness that, in the opinion of the investigator, would make participation unsuitable Any other abnormal laboratory value or intercurrent medical condition that, in the opinion of the investigator, would make participation unsuitable Known mental incapacity or language barriers precluding adequate understanding of the informed consent process and study procedures
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Receive belimumab 200mg subcutaneously once weekly for 4 weeks
Drug: Belimumab Prefilled Syringe [Benlysta]
Monoclonal antibody binding BAFF
Allocation probability
Number of potential donors in Eurotransplant region based on HLA and ABO compatibility
Time frame: 16 weeks
Belimumab-enhanced HLA-specific memory B-cell profiling
Concordance between HLA antibodies found in the serum and the supernatant of cultured peripheral blood mononuclear cells after belimumab administration.
Time frame: 16 weeks
Antibody-mediated rejection rate at 1 year
To investiage the antibody-mediated rejection rate in kidney transplant recipients of a delisted donor-specific anti-HLA antibody
Time frame: 1 year
High-sensitivity flow cytometry B-cell phenotyping
Investigate the impact of belimumab-mediated BAFF inhibition on circulating B-cell phenotype. Peripheral blood mononuclear cells will be phenotyped at day 0, day 28, and day 112. B-cell subsets are classified with the following surface markers: CD19, CD27, CD38, CD24, CD5, immunoglobulins.
Time frame: 16 weeks
Graft failure
To investigate the occurence of graft failure in the 2 years following transplantation. Graft failure is defined as a return to dialysis.
Time frame: 2 years
Single-cell RNA sequencing circulating B cells
Investigate changes in B-cell transcriptome during and after administration of belimumab. Single-cell RNA sequencing will be performed on samples from day 0, day 28, and day 112. General analysis will include DEG and FAE. Specific analysis will include analysis of proliferation signature, BCR sequencing, and analysis of GO terms relate dto migration.
Time frame: 12 weeks
Plan to share: Undecided
No publications or documents are linked to this record.
Started Apr 2026 (actual). Primary completion is estimated for Jan 2028, 21 months after the start.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Belimumab
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