Rituximab for Idiopathic Nephrotic Syndrome
Primary Purpose
Idiopathic Nephrotic Syndrome
Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Nephrotic Syndrome focused on measuring Nephrotic syndrome, Proteinuria, Rituximab
Eligibility Criteria
Inclusion Criteria:
- Age between 1 and 16 years.
- Steroid-dependent idiopatic nephrotic syndrome for a minimum of 6 to a maximum of 12 months at the time of study entry, regardless of disease duration.
- Low-dose steroid dependence (between 0.4 and 0.7 mg/ kg/ day)
Exclusion Criteria:
- Positivity of autoimmunity tests (ANA, nDNA, ANCA) or reduced C3 levels
- Histological pattern suggestive for congenital anomalies (diffuse mesangial sclerosis without IgM deposits, cystic-like tubular dilations, evidence of mithocondrial damage on electronic microscopy.
- Histological pattern not correlated with idiopathic nephrotic syndrome in the pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or localized vasculitis, amyloidosis).
- Evidence of homozygous or heterozygous mutations in podocitary genes commonly involved in the pathology (NPHS1, NPHS2, WT1).
- Estimated glomerula filtration rate (eGFR) < 60ml/min.
- Presence of circulating IgM against HCV, HBV, parvovirus or mycoplasm.
Sites / Locations
- IRCCS Giannina Gaslini Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Steroid tapering.
Rituximab
Arm Description
Single administration of Rituximab 375 mg/mq at a rate of 0.5 to 1.5 ml/min over approximately 6 hours, following the infusion of 2.5-5 mg of intravenous chlorfenamine maleate (based on the local protocol and patient tolerance), methylprednisolone (2 mg/Kg) in normal saline and oral paracetamol (8 mg/kg).
Outcomes
Primary Outcome Measures
Three months proteinuria
To be considered non-inferior, rituximab will have to allow steroid withdrawal and maintain three-month proteinuria within a pre-specified non-inferiority margin of three times the levels among controls.
Secondary Outcome Measures
Time-to-relapse mesaure
Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.
Full Information
NCT ID
NCT04494438
First Posted
July 28, 2020
Last Updated
January 2, 2023
Sponsor
Istituto Giannina Gaslini
1. Study Identification
Unique Protocol Identification Number
NCT04494438
Brief Title
Rituximab for Idiopathic Nephrotic Syndrome
Official Title
Rituximab in Patients With Low Dose Steroid-dependent Idiopathic Nephrotic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Istituto Giannina Gaslini
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Open-label, randomized, controlled trial due to value whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS.
The investigators will enroll 30 pediatric patients affected by idiopathic nephrotic syndrome, who have been in treatment with steroids for at least one year. The lowest dose of drug required to maintain a stable remission will be between 0.4 and 0.7 mg/ kg/ day.
This trial provides an initial run-in phase of one month during wich remission will be achieved by means of a standard oral prednisone course. Once remission has been achieved children will be randomized in a parallel arm open label RCT to continue prednisone alone for one month (control) or to add a single intravenous infusion of rituximab (375 mg/m2 - intervention). Prednisone will be tapered in both arms after one month.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Nephrotic Syndrome
Keywords
Nephrotic syndrome, Proteinuria, Rituximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Steroid tapering.
Arm Type
No Intervention
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Single administration of Rituximab 375 mg/mq at a rate of 0.5 to 1.5 ml/min over approximately 6 hours, following the infusion of 2.5-5 mg of intravenous chlorfenamine maleate (based on the local protocol and patient tolerance), methylprednisolone (2 mg/Kg) in normal saline and oral paracetamol (8 mg/kg).
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera, Anti CD-20 antibodies
Primary Outcome Measure Information:
Title
Three months proteinuria
Description
To be considered non-inferior, rituximab will have to allow steroid withdrawal and maintain three-month proteinuria within a pre-specified non-inferiority margin of three times the levels among controls.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Time-to-relapse mesaure
Description
Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 1 and 16 years.
Steroid-dependent idiopatic nephrotic syndrome for a minimum of 6 to a maximum of 12 months at the time of study entry, regardless of disease duration.
Low-dose steroid dependence (between 0.4 and 0.7 mg/ kg/ day)
Exclusion Criteria:
Positivity of autoimmunity tests (ANA, nDNA, ANCA) or reduced C3 levels
Histological pattern suggestive for congenital anomalies (diffuse mesangial sclerosis without IgM deposits, cystic-like tubular dilations, evidence of mithocondrial damage on electronic microscopy.
Histological pattern not correlated with idiopathic nephrotic syndrome in the pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or localized vasculitis, amyloidosis).
Evidence of homozygous or heterozygous mutations in podocitary genes commonly involved in the pathology (NPHS1, NPHS2, WT1).
Estimated glomerula filtration rate (eGFR) < 60ml/min.
Presence of circulating IgM against HCV, HBV, parvovirus or mycoplasm.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gian Marco Ghiggeri, MD
Organizational Affiliation
Istituto Giannina Gaslini
Official's Role
Study Director
Facility Information:
Facility Name
IRCCS Giannina Gaslini Institute
City
Genova
ZIP/Postal Code
16147
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
23739238
Citation
Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, Ghio L, Merscher-Gomez S, Edefonti A, Pasini A, Montini G, Murtas C, Wang X, Muruve D, Vaglio A, Martorana D, Pani A, Scolari F, Reiser J, Ghiggeri GM. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013 Nov;84(5):1025-33. doi: 10.1038/ki.2013.211. Epub 2013 Jun 5.
Results Reference
background
PubMed Identifier
17661091
Citation
Ghiggeri GM, Musante L, Candiano G, Bruschi M, Santucci L, Barbano G, Trivelli A, Rivabella L, Gusmano R, Perfumo F. Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis. Pediatr Nephrol. 2007 Nov;22(11):1953-6. doi: 10.1007/s00467-007-0550-y. Epub 2007 Jul 28.
Results Reference
background
PubMed Identifier
16672715
Citation
Pescovitz MD, Book BK, Sidner RA. Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med. 2006 May 4;354(18):1961-3. doi: 10.1056/NEJMc055495. No abstract available.
Results Reference
background
PubMed Identifier
22581994
Citation
Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, Benetti E, Murtas C, Messina G, Massella L, Porcellini MG, Montagna M, Regazzi M, Scolari F, Ghiggeri GM. Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol. 2012 Jun;23(6):1117-24. doi: 10.1681/ASN.2011080775. Epub 2012 May 10.
Results Reference
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PubMed Identifier
21566104
Citation
Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011 Jun;6(6):1308-15. doi: 10.2215/CJN.09421010. Epub 2011 May 12.
Results Reference
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PubMed Identifier
24480824
Citation
Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.
Results Reference
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PubMed Identifier
18465150
Citation
Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008 Aug;23(8):1269-79. doi: 10.1007/s00467-008-0814-1. Epub 2008 May 9.
Results Reference
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PubMed Identifier
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Citation
Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N, Egido J, Praga M; Trabajo de Enfermedades Glomerulares de la Sociedad Espanola de Nefrologia (GLOSEN). Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009 Aug;4(8):1317-23. doi: 10.2215/CJN.00570109. Epub 2009 Jul 2.
Results Reference
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Rituximab for Idiopathic Nephrotic Syndrome
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