2023-508116-32-00招募中2 期
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.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Observational phase
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Adults within the age group ≥18 and ≤75 years
- •Candidate for a kidney transplant
- •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.
- •Provided informed consent to participation in this study
- •Willingness and ability to comply with the protocol of this study
- •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.
排除标准
- •Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG, corrected for ESRD.
- •Have a neutrophil count < 1.5x10E9/L.
- •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.
- •Have a significant history of infections that in the opinion of the investigator would make the patient unsuitable for participation in the study.
- •Have a history of an anaphylactic or otherwise severe allergic reaction to parenteral administration of human or murine proteins or monoclonal antibodies.
- •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.
- •Have evidence of psychiatric illness that in the opinion of the investigator would make the patient unsuitable for participation in the study.
- •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.
- •Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities.
- •Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA <0.1 g/L).
- •Having received any vaccination within 3 months before screening.
- •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.
- •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).
- •Previous administration of high-dose corticosteroids (>50mg of prednisolone or equivalent per day) within 90 days from the screening day.
- •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.
- •Uncontrolled HIV infection as defined by CD4 count below 250 cells/mm³ and/or detectable viremia.
- •History of a primary immunodeficiency including complement-deficiencies.
结局指标
主要结局
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.
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.
次要结局
- 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.
- 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.
- The difference in concordant positive antigens in memory analysis between the two pretreatment assays and the two on-treatment assays.
- 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.
- 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.
- 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.
- The difference in serum BAFF levels in peripheral blood before, during and after belimumab treatment.
- 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.
- 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.
- 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.
研究者
A.P.J. de Vries
Scientific
Academisch Ziekenhuis Leiden
研究点 (1)
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