Nephrotic syndrome : focal and segmental glomerular lesions
Conditions
Interventions
This is an observational, open-label, prospective, single-arm clinical trial. The total sample size is expected to be 14 participants, who will be followed up for 2 years after the last plasmapheresis
V03.175.500
Sponsors
Hospital do Rim - Escola Paulista de Medicina - Universidade Federal de São Paulo
Universidade Federal de São Paulo - UNIFESP
Eligibility
Age
5 Years to 75 Years
Inclusion criteria
Inclusion criteria: Signed informed consent form. Male or female participants aged between 5 and 75 years old at the time of signing the informed consent form or informed assent form. Be able to comply with the study protocol, according to the investigator's assessment. Be a kidney transplant patient. Have a diagnosis of focal segmental glomerulosclerosis (FSGS) according to the following criteria, persistently elevated proteinuria (UPCR greater than or equal to 3 in 3 daily serial measurements without showing a 50 percent reduction in proteinuria at that time). Have a kidney biopsy before or during screening. Diagnosis should be based on light microscopy, immunofluorescence and, if possible, electron microscopy. For fertile women, agreement to remain abstinent (abstain from heterosexual intercourse) or use adequate contraception during the treatment period and for 18 months after the final dose of rituximab, a woman is considered fertile if she is postmenarchal, has not reached postmenopausal status (greater than or equal to 12 continuous months of amenorrhea with no identified cause other than menopause) and is not permanently infertile due to surgery (i.e. removal of the ovaries, fallopian tubes or uterus) or another cause as determined by the investigator (e.g. agenesis of Muller's ducts), the definition of fertile status may be adapted to standardize with local guidelines or norms. the following are examples of appropriate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormone-releasing intrauterine devices; copper intrauterine devices; male or female condom with or without spermicide and hood, diaphragm or sponge with spermicide, the reliability of sexual abstinence should be assessed in relation to the duration of the clinical study and the patient's preferred and daily lifestyle, periodic abstinence (e.g. tab methods, ovulation, methods) and coitus interruptus are not adequate contraceptive methods, if required by local guidelines or standards, locally recognized adequate contraceptive methods and information on the reliability of abstinence will be described in the local informed consent form
Exclusion criteria
Exclusion criteria: Patients with a secondary cause of Focal Segmental Glomerulosclerosis (FSGS) after kidney transplantation (e.g., rejection, infections such as hepatitis B, Systemic Lupus Erythematosus (SLE), medications, malignancies). Pregnant or breastfeeding women, or women intending to become pregnant during the study or within 18 months after the final dose of rituximab. Receipt of a live vaccine within 28 days before or during screening. Thrombocytopenia, anemia, and/or coagulopathy with a high risk of clinically significant bleeding. Significant or uncontrolled clinical disease that, in the investigator's opinion, would prevent the patient from participating. Known infection with Human Immunodeficiency Virus (HIV). Known active infection of any type, excluding fungal infection of the nail beds. Any major episode of infection requiring hospitalization or treatment with IV anti-infective treatments during the 2 months before or during screening or with oral anti-infective treatments during the 2 weeks before or during screening. History of recurrent or chronic severe infection. History of progressive multifocal leukoencephalopathy (PML). History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ, except for treated or excised and resolved non-melanoma skin carcinomas. Active alcohol or drug abuse or history of alcohol or drug abuse in the 11 months prior to screening. Intolerance or contraindication to the therapies under study, including: Evidence of intolerance or toxicity associated with rituximab prior to screening. History of severe or anaphylactic allergic reactions to monoclonal antibodies or known hypersensitivity to any component of the rituximab infusion. Intolerance or contraindication to oral or IV corticosteroids and premedications. Absence of peripheral venous access. Laboratory parameters Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2.5 x the upper limit of normal (ULN). Amylase or lipase > 2 x ULN. Neutrophils < 1.5 x 103 /uL. CD19+ B cells < 5/uL. Hepatitis B surface antigen (HbsAg) positive on screening. Patients who are HBsAg negative and positive for hepatitis B core antibody without detectable hepatitis B virus (HBV) DNA will be allowed in the study, but will require regular monitoring of hepatitis B virus (HBV) DNA. Positive antibody against hepatitis C virus (HCV) in screening. Patients with a positive test result for hepatitis C antibody without detectable hepatitis C virus (HCV) RNA for at least 12 months after completion of antiviral therapy are eligible, but will require regular monitoring of hepatitis C virus (HCV) RNA. Hemoglobin < 9 g/dL. Platelet count < 75,000/uL. Positive serum human chorionic gonadotropin measured at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| It is expected to observe a reduction in proteinuria as well as stabilization or improvement of the estimated Glomerular Filtration Rate (eGFR), which will be assessed through the criteria of partial or complete remission on the 35th day after the start of treatment. Complete remission (CR) is defined as a urine protein-to-creatinine ratio (UPCR) less than or equal to 0.3 (or 24-hour proteinuria, if a 24-hour urine collection was performed) with a stable estimated Glomerular Filtration Rate (eGFR), defined as an eGFR no more than 15% below baseline, and without concomitant events such as treatment failure or early withdrawal from the study. The eGFR is calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Partial remission (PR) is defined as a reduction of at least 50% in the urine protein-to-creatinine ratio (UPCR) from baseline and a UPCR less than or equal to 3.5 but greater than 0.3, with a stable eGFR, defined as an eGFR no more than 15% below baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| It is expected to observe a reduction in proteinuria as well as stabilization or improvement of the estimated Glomerular Filtration Rate (eGFR), which will be assessed through the criteria of partial or complete remission after the 35th day following the start of treatment. It is also expected to evaluate the proportion of patients who presented an increase in the urine protein-to-creatinine ratio (UPCR) to greater than 3.5 after achieving complete remission (CR) or partial remission (PR), and this will be classified as relapse. In addition, relapse in a patient who achieved partial remission (PR) also requires an increase greater than 50% in the urine protein-to-creatinine ratio (UPCR) to greater than 3.5 (with the 50% increase assessed from the nadir of the urine protein-to-creatinine ratio – UPCR – during partial remission – PR) or requires additional immunosuppressive therapy or a modification in such therapy. The proportion of patients with a reduction of greater than or equal to 30% in the estimated Glomerular Filtration Rate (eGFR) after the 35th day following the start of treatment will also be evaluated. It is expected to evaluate the safety of rituximab in relation to the incidence and severity of adverse events, with severity determined according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI CTCAE) version 5.0. The safety assessment will also evaluate the change from baseline in the results of clinical laboratory tests. | — |
Countries
Brazil
Contacts
Public ContactJuliana Mansur
Hospital do Rim
Outcome results
None listed