Rituximab for Idiopathic steroid-sensitive nephrotic syndrome|Nephrotic syndrome

Inclusion criteria

• {"criterion_text":"- Informed consent to participate in the study.\n- Age of at least 18 years.\n- Diagnosis of podocytopathy of the most likely primary (immune-mediated) nature, meeting all of the following criteria: a. Histopathological diagnosis of MCD (Minimal Change Disease) or FSGS (Focal Segmental Glomerulosclerosis)*; AND b. A history of good response to standard-dose glucocorticoids treatment - defined as complete remission of nephrotic syndrome within 16 weeks of treatment with prednisone at a dose of up to 1 mg/kg/day, max. 80 mg/day (or equivalent dose of another glucocorticoid) or up to 2mg/kg/48h, max. 120 mg (or equivalent dose of another glucocorticoid) preceded or not preceded by the administration of intravenous glucocorticoids; c. Excluded secondary causes of nephrotic syndrome. *It is acceptable to include a patient without or with a non-diagnostic biopsy result as long as criteria 3b and 3c are met and the disease course is typical of podocytopathy and the differential diagnosis does not support another diagnosis. Each case should be considered individually, in consultation with the Coordinating Investigator.\n- A relapsing course of disease that meets all of the following criteria: a.\tAt least 1 relapse of nephrotic syndrome in the history; b.\tLast relapse of nephrotic syndrome within 2 years prior to study inclusion that occurred during immunosuppressive therapy or within 6 months of its withdrawal.\n- Ongoing immunosuppressive treatment to maintain remission after the last relapse lasting min. 2 weeks and max. 100 weeks (patients with SD (steroid-dependence)/FR (frequent relapses)) from achieving partial or complete remission.\n- At the time of inclusion in the study, at least partial remission of disease with proteinuria < 1.0 g/day (or uPCR <1000 mg/g) achieved with treatment with glucocorticoids and/or glucocorticoids-sparing immunosuppressant."}

Exclusion criteria

• {"criterion_text":"- Probable or certain secondary cause of podocytopathy, including, but not limited to, chronic use of medications with a confirmed association with MCD (Minimal Change Disease) (e.g., lithium salts, interferon, non-steroidal anti-inflammatory drugs), paraneoplastic syndrome, podocyte protein mutations.\n- Treatment with cyclophosphamide within 6 months prior to study inclusion.\n- Treatment with rituximab within 18 months prior to study inclusion.\n- Presence of any of the contraindications to the administration of rituximab (according to the SmPC): a.\tHypersensitivity to the active substance or excipients; b.\tHypersensitivity to mouse proteins; c.\tActive infection with a severe course; d.\tSevere immunodeficiency*; e.\tPregnancy, breastfeeding, or refusal to use effective pregnancy prevention methods during the study (applies to women); f. Severe heart failure (NYHA class IV) or severe uncontrolled heart disease. g.\tPost-vaccination status with a live vaccine within 4 weeks prior to study inclusion. * Immunoglobulin G deficiency secondary to nephrotic syndrome, as well as immunoglobulin G deficiency with serum IgG levels >250 g/L without a history of severe infectious complications, should not be considered as an absolute exclusion criterion. Each case should be considered individually.\n- A positive result on any of the following virology tests: a.\tPresence of anti-HIV antibodies; b.\tPresence of anti-HCV antibodies** and HCV RNA viremia; c.\tPresence of HBs antigen. If anti-HCV antibodies are found, the patient may be eligible for the study provided that HCV RNA viremia is absent.\n- Glomerular filtration rate - eGFR less than 45 ml/min/1.73m2 according to the CKD-EPI 2021 formula.\n- Hypersensitivity to drugs used for premedication and prophylaxis of opportunistic infections, including corticosteroids, paracetamol, clemastine, cotrimoxazole (sulfamethoxazole+trimethoprim, SMX/TMP).\n- Active neoplastic disease or history of neoplastic disease in the last 5 years.\n- Any other abnormality or disease not described above that excludes the patient from the study based on the Investigator's assessment."}

Primary endpoints

• {"endpoint_text":"- Time from randomization to first relapse of nephrotic syndrome (non-inferiority hypothesis).","definition_or_measurement_approach":"Measured as time (days) from randomization to the first documented relapse of nephrotic syndrome."}

Secondary endpoints

• {"endpoint_text":"- Time from randomization to first relapse of nephrotic syndrome (superiority hypothesis).","definition_or_measurement_approach":"Measured as time (days) from randomization to first documented relapse."}
• {"endpoint_text":"- Percentage of nephrotic syndrome relapse within 24 months.","definition_or_measurement_approach":"Proportion (%) of participants experiencing relapse within 24 months after randomization."}
• {"endpoint_text":"- Cumulative dose of glucocorticoids administered within 24 months of randomization.","definition_or_measurement_approach":"Sum of glucocorticoid doses administered to each participant over 24 months post-randomization (cumulative dose)."}
• {"endpoint_text":"- Absolute values and differences from the entry assessment in the number of points obtained in the EQ-index (EQ-index) and analog scale (EQ-VAS) according to the EQ-5D-5L questionnaire at 24 months after randomization.","definition_or_measurement_approach":"EQ-5D-5L questionnaire scores (EQ-index and EQ-VAS) at 24 months and change from baseline."}
• {"endpoint_text":"- Severe adverse event rate.","definition_or_measurement_approach":"Incidence (rate) of serious adverse events during the study period."}
• {"endpoint_text":"- Rate of adverse events of special interest.","definition_or_measurement_approach":"Incidence (rate) of predefined adverse events of special interest during the study period."}

Poland

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

10-02-2025

Processing Time Days

18

Number Of Sites

12

Number Of Participants

70

Primary sponsor

Full Name

Medical University Of Lodz

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Third parties

• {"country":"","full_name":"Polish Medical Research Agency","duties_or_roles":"Source of monetary support","organisation_type":""}