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CompletedNCT04494438Updated Jan 4, 2023

Rituximab for Idiopathic Nephrotic Syndrome

A Phase 3 interventional study of Rituximab in Idiopathic Nephrotic Syndrome, sponsored by Istituto Giannina Gaslini. Completed at 1 site in Italy. Open to participants aged 1 Year to 16 Years. Per ClinicalTrials.gov, last updated 2023-01-04.

Sponsored by Istituto Giannina Gaslini · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
1 Year to 16 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Idiopathic Nephrotic Syndrome

Keywords

  • Nephrotic syndrome
  • Proteinuria
  • Rituximab
03

Who can participate

Ages eligible
1 Year to 16 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • No intervention
    Steroid tapering.
  • Experimental
    Rituximab

    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).

    Drug: Rituximab

Interventions

  • DrugRituximab

    Also known as: Mabthera, Anti CD-20 antibodies

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 3 months

Secondary outcomes

  1. Time-to-relapse mesaure

    Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.

    Time frame: 12 months

06

Study locations

1 site
  • IRCCS Giannina Gaslini Institute
    Genova, 16147, Italy
07

References and documents

Publications

  • 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. PubMed 23739238 ↗
  • 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. PubMed 17661091 ↗
  • 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. PubMed 16672715 ↗
  • 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. PubMed 22581994 ↗
  • 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. PubMed 21566104 ↗
  • 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. PubMed 24480824 ↗
  • 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. PubMed 18465150 ↗
  • 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. PubMed 19578004 ↗
08

Registry details

Key details

Study ID
NCT04494438
Lead sponsor
Istituto Giannina Gaslini
Responsible party
Gian Marco Ghiggeri MD, PhD (Principal Investigator, Istituto Giannina Gaslini) — Principal investigator
First posted
Jul 31, 2020
Start date
Jul 2013
Primary completion
Dec 2016
Completion
Dec 2016
Last update
Jan 4, 2023

Study contacts

Gian Marco Ghiggeri, MD
study director · Istituto Giannina Gaslini

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jan 2023. You cannot join it, but the record below documents what was studied.

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