BE-MOBILYZED: 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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Phenomena and Processes [G] - Immune System Phenomena [G13]

Trial duration

17 Mar 2026 → ongoing

Decision date (initial)

2025-11-27

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

GlaxoSmithKline

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate the effects of belimumab on the antigen-specificity profile of circulating HLA-specific memory B-cells in order to aid delisting for improved and safer transplant access in highly-sensitized.

Secondary objectives 10

1. To investigate the effects of a delisting strategy which accounts for circulating mobilized mBC on the probability of donor organ allocation.
2. To investigate transplant outcomes, including graft survival, rejection rates and overall patient survival in patients transplanted with donor kidneys which express HLA-specificities which were delisted as unacceptable antigen.
3. To investigate the concordance of the antigen specificity profile of circulating HLA-specific memory B-cells of tests before treatment with belimumab, compared to on-treatment.
4. To investigate the effects of belimumab on MFI levels of anti-HLA antibodies produced by supernatants of stimulated circulating memory B-cells
5. To investigate the effects of belimumab on MFI levels of anti-HLA antibodies in plasma
6. To investigate the long-term post-treatment effects of belimumab on the antigen-specificity profile of circulating HLA-specific memory B-cells.
7. To investigate the effects of belimumab on plasma BAFF levels.
8. To investigate the effects of belimumab on phenotypically distinct B-cell subsets in the peripheral circulation
9. To investigate the impact of belimumab-mediated BAFF inhibition on the transcriptional landscape of B-cells
10. To investigate the adverse event rate, serious adverse event rate and SUSAR rate of a fourweek course of subcutaneous belimumab within a population of highly-sensitized renal transplant candidates.

Conditions and MedDRA coding

Antibody-mediated rejection of renal grafts

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults within the age group ≥18 and ≤75 years
2. Candidate for a kidney transplant
3. 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.
4. Provided informed consent to participation in this study
5. Willingness and ability to comply with the protocol of this study
6. 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 17

1. Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG, corrected for ESRD.
2. Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA <0.1 g/L).
3. Having received any vaccination within 3 months before screening.
4. 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.
5. 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).
6. Previous administration of high-dose corticosteroids (>50mg of prednisolone or equivalent per day) within 90 days from the screening day.
7. 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.
8. Uncontrolled HIV infection as defined by CD4 count below 250 cells/mm³ and/or detectable viremia.
9. History of a primary immunodeficiency including complement-deficiencies.
10. Have a neutrophil count < 1.5x10E9/L.
11. 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.
12. Have a significant history of infections that in the opinion of the investigator would make the patient unsuitable for participation in the study.
13. Have a history of an anaphylactic or otherwise severe allergic reaction to parenteral administration of human or murine proteins or monoclonal antibodies.
14. 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.
15. Have evidence of psychiatric illness that in the opinion of the investigator would make the patient unsuitable for participation in the study.
16. 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.
17. Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 10

1. 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.
2. 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.
3. The difference in concordant positive antigens in memory analysis between the two pretreatment assays and the two on-treatment assays.
4. 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.
5. 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.
6. 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.
7. The difference in serum BAFF levels in peripheral blood before, during and after belimumab treatment.
8. 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.
9. 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.
10. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

A.P.J. de Vries

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

A.P.J. de Vries

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications