Belimumab to Mobilise Memory B-cells From Secondary Lymhoid Organs to Improve Memory B-cell HLA-specificity Profiling to Support Delisting for Transplant Access in Highly-sensitized

NCT07539857 | Not Yet Recruiting Phase 2

• 1 other identifier: 133738
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Kidney Transplant Rejection

Keywords

HLA; Memory B cell; Belimumab; Highly sensitized; Delisting; Kidney transplantation

Outcome Measures

Primary Outcomes (1)

• Allocation probability

  Number of potential donors in Eurotransplant region based on HLA and ABO compatibility

  16 weeks

Secondary Outcomes (5)

• Belimumab-enhanced HLA-specific memory B-cell profiling

  16 weeks

• Antibody-mediated rejection rate at 1 year

  1 year

• High-sensitivity flow cytometry B-cell phenotyping

  16 weeks

• Graft failure

  2 years

• Single-cell RNA sequencing circulating B cells

  12 weeks

Study Arms (1)

Belimumab

EXPERIMENTAL

Receive belimumab 200mg subcutaneously once weekly for 4 weeks

Drug: Belimumab Prefilled Syringe [Benlysta]

Interventions

Belimumab Prefilled Syringe [Benlysta] DRUG

Monoclonal antibody binding BAFF

Belimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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: * 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 Acceptable Mismatch (AM) program, if eligible for inclusion in this program Provision of written informed consent for participation in this study Willingness and ability to comply with the study protocol 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-childbearing potential (i.e., status post hysterectomy, postmenopausal, bilateral oophorectomy, documented bilateral tubal ligation, or other permanent sterilization procedure) Of childbearing potential and willing to use effective contraception 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 investigational 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 corticosteroids (\>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 HBsAg or HBcAb, or a positive hepatitis C antibody test without antiviral treatment Uncontrolled HIV infection, defined as CD4 count \<250 cells/mm³ and/or detectable viremia History of a primary immunodeficiency, including complement deficiencies Neutrophil count \<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 malignancy 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 metastatic 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Leiden University Medical Centre

Leiden, 2333 ZA, Netherlands

Location

MeSH Terms

Interventions

belimumab

Central Study Contacts

Simon Zethof, MD

CONTACT

071 526 91 11; s.c.zethof@lumc.nl

Aiko de Vries, MD, PhD

CONTACT

071 526 91 11; a.p.j.de_vries@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: March 31, 2026
• First Posted: April 20, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

NL (1)