NCT04494438

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jul 2013

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2013

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
3.7 years until next milestone

First Submitted

Initial submission to the registry

July 28, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 31, 2020

Completed
Last Updated

January 4, 2023

Status Verified

January 1, 2023

Enrollment Period

3.4 years

First QC Date

July 28, 2020

Last Update Submit

January 2, 2023

Conditions

Idiopathic Nephrotic Syndrome

Keywords

Nephrotic syndromeProteinuriaRituximab

Outcome Measures

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.

    3 months

Secondary Outcomes (1)

  • Time-to-relapse mesaure

    12 months

Study Arms (2)

Steroid tapering.

NO INTERVENTION

Rituximab

EXPERIMENTAL

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

RituximabDRUG
Also known as: Mabthera, Anti CD-20 antibodies
Rituximab

Eligibility Criteria

Age1 Year - 16 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS Giannina Gaslini Institute

Genova, 16147, Italy

Location

Related Publications (9)

  • 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.

    PMID: 23739238BACKGROUND

  • 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.

    PMID: 17661091BACKGROUND

  • 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.

    PMID: 16672715BACKGROUND

  • 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.

    PMID: 22581994BACKGROUND

  • 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.

    PMID: 21566104BACKGROUND

  • 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.

    PMID: 24480824BACKGROUND

  • 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.

    PMID: 18465150BACKGROUND

  • 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.

    PMID: 19578004BACKGROUND

  • 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: 39513526DERIVED

MeSH Terms

Conditions

Nephrosis, LipoidNephrotic SyndromeProteinuria

Interventions

Rituximab

Condition Hierarchy (Ancestors)

NephrosisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesUrination DisordersUrological ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Gian Marco Ghiggeri, MD

    Istituto Giannina Gaslini

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 28, 2020

First Posted

July 31, 2020

Study Start

July 1, 2013

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

January 4, 2023

Record last verified: 2023-01

Locations

IT(1)