Obinutuzumab for Idiopathic nephrotic syndrome | Steroid-dependent nephrotic syndrome | Frequently relapsing nephrotic syndrome

Inclusion criteria

• {"criterion_text":"-Age ≥ 3 and < 18 ans"}
• {"criterion_text":"-Steroid dependant Nephrotic Syndrome defined as: •\t2 or more relapses during steroids or within 2 weeks following discontinuation. •\tOR 2 or more relapses including one under steroid-sparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, levamisole) or 2 or more relapses including one under steroid-sparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, levamisole) or within 6 months following treatment withdrawal . OR Frequent Relapsing Nephrotic Syndrome defined as: •\t2 or more relapses within 6 months following first remission or 3 or more relapses within any 12-month period"}
• {"criterion_text":"-Last relapse within 3 months prior to inclusion"}
• {"criterion_text":"-In remission, defined as 3 consecutive urinary dipsticks without proteinuria, at the time of randomization"}
• {"criterion_text":"-Vaccination schedule in accordance with the current recommendations in France"}
• {"criterion_text":"-Informed consent from parents"}

Exclusion criteria

• {"criterion_text":"-Secondary cause of nephrotic syndrome (such as membranous nephropathy, IgA nephropathy, lupus nephritis)"}
• {"criterion_text":"-History of malignancy- Uncontrolled infection (viral, bacterial and fungal)"}
• {"criterion_text":"-Vaccination with a live vaccine within 4 weeks prior to assignment/randomization"}
• {"criterion_text":"-Known hyperprolinemia"}
• {"criterion_text":"-Hypersensitivity to the active substance (OBI or RTX) or to proteins of murine origin, or to any of the other excipients"}
• {"criterion_text":"-Pregnancy or breastfeeding or ability to become pregnant and refusal to use effective contraception during the 18 months following the study treatment (only 1 infusion of obinutuzumab/Rituximab at the beginning of the study)"}
• {"criterion_text":"-Patient without medical insurance coverage (beneficiary or legal)"}
• {"criterion_text":"-Primary or secondary steroid resistance nephrotic syndrome"}
• {"criterion_text":"-Prior treatment with Rituximab within 6 months"}
• {"criterion_text":"-Prior treatment with obinutuzumab at any time"}
• {"criterion_text":"-CD20+ B-cell count < 2.5%"}
• {"criterion_text":"-Patient with neutrophils < 1.5 G/L and/or platelets < 75 G/L"}
• {"criterion_text":"-GFR < 80 ml/min/1.73m2"}
• {"criterion_text":"-Weight <16kg"}
• {"criterion_text":"-History of severe infection such as tuberculosis, hepatitis B, hepatitis C or HIV infection or LEMP"}

Primary endpoints

• {"endpoint_text":"-The primary outcome is the occurrence of a relapse defined as a 3+ proteinuria on dipstick on 3 consecutive days, with 1 laboratory urine dosage of Protein-over-creatinine ratio > 0.20g/mmol (> 0.2g/g), within 12 months following the initiation of Treatment.","definition_or_measurement_approach":"Relapse defined by 3+ proteinuria on dipstick for 3 consecutive days plus laboratory urine protein/creatinine ratio > 0.20 g/mmol (> 0.2 g/g), assessed within 12 months following initiation of treatment."}

Secondary endpoints

• {"endpoint_text":"-To assess the superiority of obinutuzumab compared to rituximab on the relapse-free survival at 24-months","definition_or_measurement_approach":""}
• {"endpoint_text":"-To compare the duration of B-cell depletion after OBI and RTX","definition_or_measurement_approach":""}
• {"endpoint_text":"-To compare the relapse-free survival after B-cell recovery after OBI and RTX","definition_or_measurement_approach":""}
• {"endpoint_text":"-To compare the number of relapses, steroid courses and second line treatment strategies required within 24 months in both arms","definition_or_measurement_approach":""}
• {"endpoint_text":"-To compare the safety of the two treatments including infusion-related reactions, infections, levels of immunoglobulins, neutropenia","definition_or_measurement_approach":""}
• {"endpoint_text":"-To assess the factors associated with sustained remission","definition_or_measurement_approach":""}
• {"endpoint_text":"-To assess the cost-effectiveness of the OBI strategy","definition_or_measurement_approach":""}
• {"endpoint_text":"-To assess the budgetary impact of the generalization of the OBI strategy","definition_or_measurement_approach":""}
• {"endpoint_text":"-To assess pharmacokinetics of Obinutuzumab and Rituximab","definition_or_measurement_approach":""}
• {"endpoint_text":"-To assess the development of antidrug antibodies","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

18-04-2025

Processing Time Days

178

Number Of Sites

13

Number Of Participants

88

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"French Ministray of Health (PHRC-20)","duties_or_roles":"Source of monetary support (PHRC-20)","organisation_type":""}