Belimumab for Systemic lupus erythematosus

Inclusion criteria

• {"criterion_text":"- \tSLE patients who: 1.\tfulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria"}
• {"criterion_text":"- \tSLE patients who: 2.\thave a SLEDAI-2K score ≥6"}
• {"criterion_text":"- \tSLE patients who: 3.\tactive joint disease (arthritis) in wrist, knee or ankle joints (optional)"}
• {"criterion_text":"- \tSLE patients who: 4.\tare aged between 18-75"}
• {"criterion_text":"- \tSLE patients who: 5.\tstart with belimumab"}
• {"criterion_text":"- For comparison reasons, we will also include 5 SLE patients who do not start belimumab but receive intensified treatment with other drugs (i.e. steroids or DMARDs) to discriminate belimumab-specific effects from general immunosuppressive effects."}
• {"criterion_text":"- Patients are allowed to use stable dosages or concomitant medication such as hydroxychloroquine, azathioprine, and/or low dose steroids (<10 mg), as well as medication of therapeutic classes other than immunosuppressants."}
• {"criterion_text":"- All patients will be counseled to use appropriate contraceptive measures as is done routinely in clinical care when prescribing these type of medications"}

Exclusion criteria

• {"criterion_text":"- \tPatients who are not able to give informed consent."}
• {"criterion_text":"- \tPregnancy"}
• {"criterion_text":"- \tSevere renal impairment (eGFR <30ml/min/1.73m2)"}
• {"criterion_text":"- \tActive nephritis"}
• {"criterion_text":"- \tPresent or previous treatment with any cell depleting therapies, including anti-B-cell therapy or other investigational agents (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131). Investigational agent applies to any drug not approved for sale in the country in which it is being used."}
• {"criterion_text":"- \t90 days prior to belimumab: •\tIntravenous cyclophosphamide"}
• {"criterion_text":"- \t30 Days Prior to belimumab (or 5 half-lives, whichever is greater) •\tAny non-biologic investigational agent. Investigational agent applies to any drug not approved for sale in the country in which it is being use"}
• {"criterion_text":"- \tLive vaccines within 30 days prior to baseline or concurrently with belimumab"}
• {"criterion_text":"- \tPresence of any other disease for which study subjects need chronic or intermittent immunosuppressive therapy (e.g. prednisolon for COPD)."}
• {"criterion_text":"- \tHistory of infection: •\tCurrently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria)"}
• {"criterion_text":"- \tHistory of infection: •\tHospitalization for treatment of infection within 60 days of Day 0."}
• {"criterion_text":"- \tHistory of infection: •\tUse of parenteral (IV or IM) antibiotics (anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60 days of Day 0"}
• {"criterion_text":"- \tHistory of malignancies neoplasm within the last 5 years except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years"}
• {"criterion_text":"- \tHave any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study, including evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, poses a significant suicide risk"}
• {"criterion_text":"- \tHave a history of a primary immunodeficiency, including significant IgG deficiency (IgG level < 400 mg/dL) or IgA deficiency (IgA level < 10 mg/dL)"}
• {"criterion_text":"- \tHave current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0"}
• {"criterion_text":"- \tHave a historically positive HIV test or test positive at screening for HIV"}
• {"criterion_text":"- \tHepatitis status: •\tSerologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows: patients positive for HBsAg or HBcAb are excluded"}
• {"criterion_text":"- \tHepatitis status: •\tPositive test for Hepatitis C antibody"}
• {"criterion_text":"- \tHave a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies"}
• {"criterion_text":"- \tHave any other clinically significant abnormal laboratory value in the opinion of the investigator"}

Primary endpoints

• {"endpoint_text":"- the change in the composition of B lineage cells in the peripheral blood and lymph nodes. These will be separate co-primary endpoints. We will investigate the differences between SLE patients treated with belimumab compared to SLE patients treated with other drugs, expecting a more profound effect in patients treated with belimumab.","definition_or_measurement_approach":"Assess change in composition of B-lineage cells in peripheral blood and in lymph nodes; compare belimumab-treated SLE patients to SLE patients treated with other drugs to detect a more profound effect with belimumab."}

Secondary endpoints

• {"endpoint_text":"- Correlation between changes in B lineage cells in peripheral blood/tissues and clinical response. Alterations in the B cell lineage will be related to clinical response (defined as a >4 point improvement in cSLEDAI or any improvement in BILAG-2004 score) in a 2x2 chi-square test for all patients. Further secondary and exploratory outcomes are changes in B lineage cells and associated (pathogenic) T cell subsets in lymph nodes of SLE patients in comparison to the changes in the peripheral blood","definition_or_measurement_approach":"Clinical response defined as a >4 point improvement in cSLEDAI or any improvement in BILAG-2004 score; correlation tested using a 2x2 chi-square test. Additional outcomes include changes in B-lineage and T-cell subsets in lymph nodes versus peripheral blood."}

Netherlands

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

25-11-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands