Childhood Onset Idiopathic Nephrotic Syndrome MedDRA version: 21.1 Level: PT Classification code 10029164 Term: Nephrotic syndrome System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Must be age >= 2-25 years old • Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years • Must be in complete remission defined by the absence of edema, urinary protein to creatinine ratio (UPCR) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Secondary nephrotic syndrome • History of steroid resistant nephrotic syndrome • History of genetic defects known to directly cause nephrotic syndrome • Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization • Pregnancy or breastfeeding or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab, or within 6 weeks after the final dose of MMF • Females of childbearing potential, including those who have had tubal ligation, must have a negative serum pregnancy test result within 28 days prior to initiation of study treatment and a negative urine pregnancy test at Day 1, prior to randomization • History of organ or bone marrow transplant • Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug • Intolerance or contraindication to study therapies, including any of the following: o History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion o Lack of peripheral venous access o Intolerance or contraindication to oral or intravenous (IV) corticosteroids o Intolerance or contraindication to MMF • Patients demonstrating prior treatment failure to MMF as defined by two or more relapses in any 6-month period of time while receiving MMF for at least a 6-month duration • Participants in the judgment of the investigator likely to require systemic corticosteroids for reasons other than idiopathic nephrotic syndrome during the study • Receipt of any of the following excluded therapies: o Cyclophosphamide, levamisole, mizoribine, tacrolimus, cyclosporine, or voclosporin during the 2 months prior to screening or during screening o Any biologic B cell-depleting therapy (e.g., antiCD19, antiCD20, antiCD22, such as, but not limited to, rituximab, ocrelizumab, or ofatumumab within 9 months prior to the Day 1 baseline visit. o Any biologic therapy (other than antiCD19, antiCD20, antiCD22) such as, but not limited to belimumab, daratumumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening o Oral inhibitors of Janus associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening o Any live vaccine during the 28 days prior to screening or during screening • Active infection of any kind or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization • History of or currently active primary or secondary immunodeficiency, including known history of human immunodeficiency virus (HIV) infection and other severe Immunodeficiency blood disorders • History of progressive multifocal leukoencephalopathy • History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years • Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening • High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of obinutuzumab compared with MMF based on proportion of Participants with Sustained Complete Remission at 1 year (UPCR 14 days in a 30-day period after Week 8 3.Initiation of any rescue therapy for INS, as determined by the investigator’s best medical judgment, other than systemic corticosteroids at any time after randomization 4.Treatment discontinuation due to lack of efficacy at any time after randomization 5.Death at any time after randomization ;Timepoint(s) of evaluation of this end point: 1. Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall relapse free survival (RFS) 2. Probability of RFS at Week 52 3. Cumulative corticosteroid dose (prednisone or equivalent adjusted for time on study) 4. Number of relapses 5. Proportion of participants experiencing edema associated relapse during the 52-week treatment period 6. Proportion of patients with sustained complete remission at Week 76 7. Mean change in “General Fatigue” domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue scale total score from baseline to Week 52 8. Mean change in “Physical Functioning” domain of PedsQL Quality of Life Inventory from baseline to Week 52 9. Mean change in Cure Glomerulonephropathy Network (CureGN) Edema Scale from baseline over time to Week 52 10. Incidence, nature, and severity of adverse events, with severity determined according to AE intensity (mild, moderate, severe, life-threatening) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading if applicable from baseline to Week 52 11. Incidence of laboratory or vital sign abnormalities from baseline to Week 52 12. Serum concentrations of obinutuzumab at specified timepoints 13. Proportion of participants achieving B cell depletion [highly sensitive flow cytometry (HSFC)] at specified timepoints 14. Total peripheral B cell and B cell subsets (e.g., memory B cells) counts and change from baseline at specified timepoints ;Timepoint(s) of evaluation of this end point: 1.-5. At Week 52 6. At Week 76 7-11. Baseline to Week 52 12. At Days 1, 15 28, 84, 168, 182, 224, 364, and at early study discontinuation visit 13-14. At Days 1, 15, 28, 84, 168, 224, 364 and at early study discontinuation | — |
Countries
Belgium, Brazil, France, Germany, Italy, Poland, Spain, Turkey, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed