BELIMUMAB for Antibody-mediated rejection (kidney transplant)|High HLA sensitization (transplant candidates)

Inclusion criteria

• {"criterion_text":"- Adults within the age group ≥18 and ≤75 years\n- Candidate for a kidney transplant\n- Highly-sensitized as determined by either: ≤2% probability of being matched with a donor organ within the Eurotransplant Kidney Allocation System (ETKAS) OR ≤0,5 % probability of being matched with a donor organ within the Eurotransplant AM-program, if patients qualify to be included in this program.\n- Provided informed consent to participation in this study\n- Willingness and ability to comply with the protocol of this study\n- Female subjects are eligible to enter the study if they are:Not pregnant or nursing, as indicated by a negative pregnancy test at screening. OR Of non-child-bearing potential (i.e. after hysterectomy, postmenopausal, bilateral ovariectomy or documented bilateral tubal ligation or other permanent female sterilization procedure) OR In agreement to not become pregnant in case she is of child-bearing potential and use proper contraception."}

Exclusion criteria

• {"criterion_text":"- Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG, corrected for ESRD.\n- Have a neutrophil count < 1.5x10E9/L.\n- Have a current indication for a blood product transfusion at the time of screening or have a high likelihood that a patient may require a blood transfusion during the treatment phase of this study, in the opinion of the investigator.\n- Have a significant history of infections that in the opinion of the investigator would make the patient unsuitable for participation in the study.\n- Have a history of an anaphylactic or otherwise severe allergic reaction to parenteral administration of human or murine proteins or monoclonal antibodies.\n- Have an active malignant neoplasm or a history of one in the last 5 years, with the exception of basal cell or squamous cell carcinoma of the skin which was treated with local resection only or carcinoma in situ of the uterine cervix treated locally with no evidence of metastatic disease for 3 years.\n- Have evidence of psychiatric illness that in the opinion of the investigator would make the patient unsuitable for participation in the study.\n- Have any other abnormal laboratory value or intercurrent medical illness that in the opinion of the investigator would make the patient unsuitable for participation in the study.\n- Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities.\n- Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA <0.1 g/L).\n- Having received any vaccination within 3 months before screening.\n- Enrolled in another clinical trial investigating an investigational drug or device at the time of belimumab treatment and delisting. However, participation in a desensitisation trial after the primary outcome is assessed is allowed.\n- Previous administration of any of the following agents within 365 days from the screening day: 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), IL6-inhibitors or IL6-IL6R modulators (e.g. Tocilizumab, Clazakizumab), Proteosome inhibitors (e.g. Bortezomib).\n- Previous administration of high-dose corticosteroids (>50mg of prednisolone or equivalent per day) within 90 days from the screening day.\n- Active infection at time of screening with any of the following: Hospitalization for treatment within previous 30 days from the screening day. OR Current use of parenteral (intravenous or intramuscular) antibiotics (including anti-bacterial, anti-viral, anti-fungal or anti-parasitic agents). OR Current serologic evidence of viral hepatitis defined as: patients positive for HbsAg or HBcAb or a positive hepatitis C antibody test not treated with antiviral medication.\n- Uncontrolled HIV infection as defined by CD4 count below 250 cells/mm³ and/or detectable viremia.\n- History of a primary immunodeficiency including complement-deficiencies."}

Primary endpoints

• {"endpoint_text":"- The difference between baseline and after 4 weeks of belimumab therapy in the number of HLA-specificities with targeted antibodies as produced by supernatants of stimulated memory B-cells, detected through Luminex single antigen bead analysis.","definition_or_measurement_approach":"Change from baseline to 4 weeks in the number of HLA-specificities with targeted antibodies measured in supernatants of stimulated memory B-cells using Luminex single antigen bead (SAB) analysis."}

Secondary endpoints

• {"endpoint_text":"- The difference between baseline and after delisting in the number of unacceptable HLAspecificities, the vPRA and the frequency of matching donors within the Eurotransplant region, as calculated through online available Eurotransplant calculator tools.\n- The number of rejection, DSA development, graft loss or mortality events in patients who were transplanted after the delisting procedure as described in this protocol has taken place.\n- The difference in concordant positive antigens in memory analysis between the two pretreatment assays and the two on-treatment assays.\n- The difference between baseline and after 4 weeks of belimumab therapy in the MFI levels of targeted antibodies as produced by supernatants of stimulated memory B-cells, detected through Luminex SAB analysis.\n- The difference between baseline and after 4 weeks of belimumab therapy in the MFI levels of targeted antibodies in plasma, detected through Luminex SAB analysis.\n- The difference between 4 weeks of belimumab therapy and 12 and 36 weeks thereafter in the number of HLA-specificity specificities with targeted antibodies as produced by supernatants of stimulated memory B-cells, detected through Luminex SAB analysis.\n- The difference in serum BAFF levels in peripheral blood before, during and after belimumab treatment.\n- The difference in phenotypically distinct B-cell subsets in the peripheral circulation at baseline, during 4 weeks of belimumab treatment and 36 weeks thereafter, as measured through flow-cytometry and ELISPOT assays.\n- Differential gene expression and pathway enrichment analysis of sorted B-cell populations (e.g., CD19⁺CD27⁺ B cells) at baseline, during 4 weeks of belimumab treatment and 36 weeks thereafter.\n- The number of adverse events, as defined in Chapter 13, during 4 weeks of belimumab treatment until 84 days thereafter. Adverse events that have led to (temporary) discontinuation of the treatment, as defined by the stop criteria mentioned in paragraph 12.3.1, will be described separately. The number of serious adverse advents during 4 weeks of belimumab treatment and 40 weeks thereafter. All SUSARs until the end of study.","definition_or_measurement_approach":"1) Changes in unacceptable HLA specificities, vPRA, and donor match frequency calculated using Eurotransplant online calculator tools. 2) Clinical events (rejection, DSA development, graft loss, mortality) recorded per protocol. 3) Concordance of positive antigens in memory B-cell assays pre- and on-treatment assessed by specified laboratory assays. 4) MFI levels in supernatants measured by Luminex SAB. 5) Plasma antibody MFI measured by Luminex SAB. 6) Longitudinal changes at 12 and 36 weeks post-treatment measured by Luminex SAB. 7) Serum BAFF levels measured in peripheral blood (assay unspecified). 8) B-cell subset phenotyping by flow cytometry and functional assays including ELISPOT. 9) RNA sequencing/differential gene expression and pathway enrichment on sorted B-cell populations. 10) Adverse events, SAEs and SUSARs captured and reported per protocol definitions (Chapter 13) over specified follow-up windows."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-11-2025

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

28

Number Of Sites

1

Number Of Participants

25

Primary sponsor

Full Name

Academisch Ziekenhuis Leiden

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"GlaxoSmithKline","duties_or_roles":"Source of monetary support","organisation_type":""}