NEPHROTIC SYNDROME MedDRA version: 21.1 Level: PT Classification code 10029164 Term: Nephrotic syndrome System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Trade Name: MabThera 100mg, concentrate for solution for infusion
Product Name: MabThera 100mg concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
Pharmace
Sponsors
MEDICAL UNIVERSITY OF GDANSK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be included in the study if he or she meets the following inclusion criteria: 1. Expresses the willingness to participate in the study and after obtaining information about the study, the patient / legal guardians will sign an informed consent form for participation in the study 2. Age at study entry> 2 years (> 24 months of age) and under 16 years of age 3. Meet the criteria for diagnosis of idiopathic steroid-dependent nephrotic syndrome (two relapses during steroid dose reduction or within two weeks of stopping steroid therapy) or nephrotic syndrome with frequent relapses (two or more relapses in 6 months or four or more relapses in a period of 12 months) 4. Remission of NS immediately prior to study entry, defined as the absence or trace of protein in the urinalysis [uPCR =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous use of immunosuppressants such as cyclophosphamide, cyclosporin A, tacrolimus, mycophenolate mofetil, levamisole 2. Diagnosis of steroid-resistant NS, nephritic syndrome or secondary NS 3. Previous severe infection (tuberculosis, systemic mycosis), HIV, HCV, HBV infection 4. Active infection 5. Severe heart diseases (heart failure, myocardial infarction, severe heart rhythm disturbances) 6. Vaccinations with live vaccines within 4 weeks prior to study inclusion 7. Poorly controlled hypertension 8. Abnormal kidney function (eGFR <90 ml / min) 9. Autoimmune disease (IgA vasculitis, systemic lupus) 10. Current or history of cancer 11. Status after organ transplantation 12. Allergy to methylprednisolone, paracetamol, cetirizine, co-trimoxazole 13. Laboratory abnormalities: leukocyte count <3000 / µl, neutrocyte count <1500 / µl, platelet count <75,000 / µl, severe liver dysfunction: ALT or AST 2.5 times upper limit of normal 14. Prior treatment with monoclonal antibodies 15. Use of another study drug within the 6 months prior to study entry, or participation in other studies at screening 16. Severe immunodeficiency 17. Pregnancy, breastfeeding or refusal to use methods of contraception in case of the ability to become pregnant (pregnancy test required - beta hCG in the blood serum at enrollment in the study) 18. Hypersensitivity to the active substance, murine proteins or to any of the excipients of the test drug (i.e. sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of the duration of disease remission in the study group compared to placebo;Secondary Objective: 1. Assessment of treatment failure in the study group compared to placebo 2. Assessment of the total dose of steroids administered in the test group compared to placebo 3. Assessment of B-cell depletion as an indicator of the risk of recurrence in the study group compared to placebo 4. Assessment of the duration of remission in the unblinded phase of the study 5. Optimizing RTX dosing 6. Assessment of the impact of the presence of anti-RTX antibodies on the effectiveness and presence of allergic reactions 7. Assessment of the effect of hypogammaglobulinemia on the duration of remission in the study group compared to placebo 8. Understanding the risk factors for the disease and how to respond to treatment with steroid-dependent NS;Primary end point(s): Relapse-free time (defined as proteinuria persisting = 3 days during the blinded phase (days 1 to 365));Timepoint(s) of evaluation of this end point: From the time of randomization to the time of first relapse after study drug administration (1-365 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1.12 months 2. Day1(before administration),2,8 (before administration), 9,29,85,169, 365,relapse* 3. From the time of study drug administration after relapse until the next relapse (1-365 days) 4.a, b. Day1 (before and after administration), 2,8(before and after administration), 9,29,85,169,365,relapse* c. Day1 (before and after administration), 2,8(before and after administration), 9, relapse* 5. Day1 (before and after administration), 2,8(before and after administration), 9,29,85,169,365,relapse* 6. Day -1,7,29,57,85,113,141,169,197,253,309,365,relapse* 7.a. Day 29 b. Day1(before administration),2,8 (before administration), 9,29,85,169, 365, relapse* c. Day1(before administration),2,8 (before administration), 9,29,85,169, 365, relapse* *first relapse in the blind and open phase;Secondary end point(s): 1. Total dose of steroids administered 2. Time from resolution of depletion to relapse 3. Relapse-free time during the unblinded phase (from the study drug administration to the 365 observation day) 4. a. Pharmacokinetics of RTX b. Correlation of RTX concentration with disease relapse c. Assessment of C4d, sC5b-9 (TCC) concentration and serum CDC activity 5. Correlation of anti-RTX antibodies with therapy failure Correlation of the presence of anti-RTX antibodies with allergic symptoms 6. Correlation of serum immunoglobulin levels with the presence of proteinuria Correlation of serum immunoglobulin levels with the presence of infection 7.a. Patient genotype determination (genome wide association study, GWAS) b. Determination of the immunophenotype of patients (subpopulations of B and T lymphocytes) c. Cytokine determination | — |
Countries
Poland
Contacts
Public ContactTrial coordinator - A. Zurowska
MEDICAL UNIVERSITY OF GDANSK
Outcome results
None listed