Ignite Creation Date:
2025-12-24 @ 5:25 PM
Ignite Modification Date:
2026-01-01 @ 4:12 PM
Study NCT ID:
NCT05786768
Status:
RECRUITING
Last Update Posted:
2023-11-09
First Post:
2023-02-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009404', 'term': 'Nephrotic Syndrome'}], 'ancestors': [{'id': 'D009401', 'term': 'Nephrosis'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 88}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-10-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-01', 'completionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-11-08', 'studyFirstSubmitDate': '2023-02-10', 'studyFirstSubmitQcDate': '2023-03-14', 'lastUpdatePostDateStruct': {'date': '2023-11-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-03-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-10-18', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Occurrence of a relapse within 12 months following the initiation of treatment', 'timeFrame': '12 months', 'description': 'Relapse is defined as a protein to creatinine ratio of 2 g/g of creatinine (0.20 g/mmol) or higher'}], 'secondaryOutcomes': [{'measure': 'Occurrence of a relapse within 24 months', 'timeFrame': '24 months'}, {'measure': 'Time to B-cell depletion', 'timeFrame': '24 months'}, {'measure': 'Duration of relapse-free survival after B-cell reconstitution', 'timeFrame': '24 months'}, {'measure': 'Cumulative steroid courses and second line immunosuppressive treatments in patients with relape', 'timeFrame': '24 months'}, {'measure': 'Safety associated with drug infusion', 'timeFrame': '24 months', 'description': 'Nature, frequency and timing of side effects'}, {'measure': 'Efficiency defined as incremental cost-effectiveness ratio in cost per relapse prevented', 'timeFrame': '24 months'}, {'measure': 'Budgetary impact defined as costs and health gains incurred with the generalization of the obinutuzumab strategy', 'timeFrame': '24 months'}, {'measure': 'Detection of Antidrug Antibodies', 'timeFrame': '24 months'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Rituximab', 'Obinutuzumab', 'Anti-Drug Antibodies'], 'conditions': ['Steroid-Dependent Nephrotic Syndrome', 'Steroid-Sensitive Nephrotic Syndrome']}, 'referencesModule': {'references': [{'pmid': '39513526', 'type': 'DERIVED', 'citation': 'Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.'}, {'pmid': '37678236', 'type': 'DERIVED', 'citation': 'Dossier C, Bonneric S, Baudouin V, Kwon T, Prim B, Cambier A, Couderc A, Moreau C, Deschenes G, Hogan J. Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1555-1562. doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.'}]}, 'descriptionModule': {'briefSummary': 'B-cell depletion with rituximab induces sustained remission in children with Steroid-Dependent or Frequent Relapsing Nephrotic Syndrome (SD/FRNS). However, most patients relapse after B-cell recovery and some do not achieve B-cell depletion. Obinutuzumab is a 2nd generation humanized monoclonal antiCD20 antibody, with enhanced B cell-depleting potential. It has been reported safe and efficient in different renal autoimmune diseases including childhood nephrotic syndrome. This double-blind, randomized multicenter study is designed to assess the efficacy and safety of a single infusion of low-dose obinutuzumab compared to a single infusion of rituximab in children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).', 'detailedDescription': 'Idiopathic nephrotic syndrome (INS) is the most frequent acquired glomerulopathy in children. The initial treatment relies on steroids, which enables remission of proteinuria in 90% of children. However, 80 % of steroid-sensitive patients will relapse, and 2/3 will become steroid-dependant with a long lasting disease over years. In this situation, immunosuppressive drugs are added as steroid-sparing agents. There is no international consensus on the second line treatment strategy after initial steroid therapy. RCT have demonstrated the efficacy of rituximab (RTX) to maintain remission in FR/SDNS after oral treatments withdrawal, however most patients relapse within 2 years, and some patients are resistant or allergic to Rituximab. Obinutuzumab (OBI) is a second generation antiCD20 mAb, that has been designed to overcome rituximab resistance in B-cell malignancies. Additional mechanisms of rituximab failure support the hypothesis that B-cell depletion could be optimized with OBI in autoimmune diseases. OBI has met its primary endpoint in lupus nephritis and a few randomized controlled trials are currently ongoing in nephrology for lupus nephritis and membranous nephropathy. We believe that a single infusion of OBI could reduce the risk of subsequent relapse in FR/SDNS and the cumulative exposure to immunosuppressive drugs.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age between 3 and 18 years\n* Steroid dependant Nephrotic Syndrome defined as:\n\n * 2 or more relapses during steroids or within 2 weeks following discontinuation.\n * 2 or more relapses including one under steroid-sparing agent (MMF, Calcineurin inhibitors, cyclophosphamide, levamisole) or within 6 months following treatment withdrawal\n\nOR Frequent Relapsing Nephrotic Syndrome defined as:\n\n* 2 or more relapses within 6 months following first remission\n* 3 or more relapses within any 12-month period\n\n * Last relapse within 3 months prior to inclusion\n * In remission, defined as 3 consecutive urinary dipsticks without proteinuria, at the time of randomization\n * Vaccination schedule in accordance with the current recommendations in France\n * Informed consent from parents\n\nExclusion Criteria:\n\n* Secondary cause of nephrotic syndrome (such as membranous nephropathy, IgA nephropathy, lupus nephritis)\n* Primary or secondary steroid resistance nephrotic syndrome\n* Prior treatment with Rituximab within 6 months\n* Prior treatment with obinutuzumab at any time\n* CD20+ B-cell count \\< 2.5%\n* Patient with neutrophils \\< 1.5 G/L and/or platelets \\< 75 G/L\n* GFR \\< 80 ml/min/1.73m2\n* Weight \\<16kg\n* History of severe infection such as tuberculosis, hepatitis B, hepatitis C or HIV infection or LEMP\n* History of malignancy- Uncontrolled infection (viral, bacterial and fungal)\n* Vaccination with a live vaccine within 4 weeks prior to assignment/randomization\n* Known hyperprolinemia\n* Hypersensitivity to the active substance (OBI or RTX) or to proteins of murine origin, or to any of the other excipients\n* 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)\n* Patient without medical insurance coverage (beneficiary or legal)'}, 'identificationModule': {'nctId': 'NCT05786768', 'acronym': 'OBIRINS', 'briefTitle': 'Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Efficacy and Safety of Obinutuzumab Versus Rituximab in Childhood Steroid Dependant and Frequent Relapsing Nephrotic Syndrome : a Double-blind Multicenter Randomized Controlled Study', 'orgStudyIdInfo': {'id': 'APHP211038'}, 'secondaryIdInfos': [{'id': '2022-003336-59', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Rituximab 375 mg/m2', 'description': 'single infusion of Rituximab (375 mg/m2)', 'interventionNames': ['Drug: single infusion of Rituximab']}, {'type': 'EXPERIMENTAL', 'label': 'Obinutuzumab 300 mg/1.73 m2', 'description': 'single infusion of Obinutuzumab 300 mg/1.73 m2', 'interventionNames': ['Drug: single infusion of Obinutuzumab']}], 'interventions': [{'name': 'single infusion of Rituximab', 'type': 'DRUG', 'otherNames': ['single infusion of Rituximab 375 mg/m2'], 'description': 'single infusion of Rituximab 375 mg/m2', 'armGroupLabels': ['Rituximab 375 mg/m2']}, {'name': 'single infusion of Obinutuzumab', 'type': 'DRUG', 'otherNames': ['single infusion of Obinutuzumab 300mg/1.73 m2'], 'description': 'single infusion of Obinutuzumab 300mg/1.73 m2', 'armGroupLabels': ['Obinutuzumab 300 mg/1.73 m2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75019', 'city': 'Paris', 'status': 'RECRUITING', 'country': 'France', 'contacts': [{'name': 'Claire DOSSIER, MD', 'role': 'CONTACT', 'email': 'claire.dossier@aphp.fr', 'phone': '+33140032467'}, {'name': 'Julien HOGAN, MD PhD', 'role': 'CONTACT', 'email': 'julien.hogan2@aphp.fr', 'phone': '+33140032142'}], 'facility': 'Robert Debre Hospital', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'centralContacts': [{'name': 'Claire DOSSIER, MD', 'role': 'CONTACT', 'email': 'claire.dossier@aphp.fr', 'phone': '+33140032467'}, {'name': 'Julien HOGAN, MD PhD', 'role': 'CONTACT', 'email': 'julien.hogan2@aphp.fr', 'phone': '+33140032142'}], 'overallOfficials': [{'name': 'Claire DOSSIER, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'ICF'], 'timeFrame': '48 months', 'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}