Rituximab for Systemic lupus erythematosus

Inclusion criteria

• {"criterion_text":"- fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria"}
• {"criterion_text":"- have a SLEDAI-2K score ≥6"}
• {"criterion_text":"- are aged between 18-75"}
• {"criterion_text":"- are clinically determined to have severity of disease and refractoriness that supports the off-label use of anti-CD20 therapy"}

Exclusion criteria

• {"criterion_text":"- Patients who are not able to give informed consent."}
• {"criterion_text":"- Pregnancy"}
• {"criterion_text":"- Severe renal impairment (eGFR <30ml/min/1.73m2 according to CKD-EPI formula)"}
• {"criterion_text":"- Present or previous treatment with any cell depleting therapies, including anti-B-cell therapy, belimumab or other investigational agents (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131) in the last 3 years. Investigational agent applies to any drug not approved for sale in the country in which it is being used."}
• {"criterion_text":"- 90 days prior to anti-CD20 therapy: •\tIntravenous cyclophosphamide"}
• {"criterion_text":"- 30 Days Prior to anti-CD20 therapy (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":"- Live vaccines within 30 days prior to baseline or concurrently with anti-CD20 therapy"}
• {"criterion_text":"- Presence of any other disease for which study subjects need chronic or intermittent immunosuppressive therapy (e.g. prednisolon for COPD)."}
• {"criterion_text":"- History 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":"- History of infection: •\tHospitalization for treatment of infection within 60 days of Day 0."}
• {"criterion_text":"- History 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":"- History 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":"- Have 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":"- Have 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":"- Have 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":"- Have a historically positive HIV test or test positive at screening for HIV"}
• {"criterion_text":"- Hepatitis 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":"- Hepatitis status: •\tPositive test for Hepatitis C antibody"}
• {"criterion_text":"- Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies"}
• {"criterion_text":"- Have any other clinically significant abnormal laboratory value in the opinion of the investigator"}

Primary endpoints

• {"endpoint_text":"- the proportion of patients with depletion of total CD19+ B cells in the peripheral blood (quantitative using highly-sensitivity flow cytometry) and lymph nodes, defined as a decrease of >2 points on a 4-point semi-quantitative scale. These will be separate co-primary endpoints. We will statistically test the difference in the proportions of patients with depletion by these criteria in RTX- versus OBI-treated patients,","definition_or_measurement_approach":"Depletion measured quantitatively in peripheral blood using high-sensitivity flow cytometry and in lymph nodes using a 4-point semi-quantitative scale; depletion defined as a decrease of >2 points. Separate co-primary endpoints for blood and lymph nodes; comparison of proportions between RTX and OBI arms."}

Secondary endpoints

• {"endpoint_text":"- Correlation between CD19+ lymphocyte (and other B lineage cells) depletion in peripheral blood/tissues and clinical response. Depletion (defined as a decrease of >2 points on a 4-point semi-quantitative scale of CD19+ cells in the lymph node) 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 20 patients. Changes in B lineage cells and associated T cell subsets in lymph nodes and skin of SLE","definition_or_measurement_approach":"Depletion defined as decrease of >2 points on 4-point semi-quantitative scale in lymph node; clinical response defined as >4 point improvement in cSLEDAI or any improvement in BILAG-2004 score; relationship tested with 2x2 chi-square for all 20 patients. Additional measurements: changes in B lineage cells and associated T cell subsets in lymph nodes and skin."}

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

20

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands