Clinical trial NCT04494438: Rituximab for Idiopathic Nephrotic Syndrome
Official title: Rituximab in Patients With Low Dose Steroid-dependent Idiopathic Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Nephrotic Syndrome
Keywords: Nephrotic syndrome
Proteinuria
Rituximab
Lead sponsor: Istituto Giannina Gaslini
Sponsor class: OTHER
First posted: 2020-07-31
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Three months proteinuria
timeFrame: 3 months
Secondary outcomes:
measure: Time-to-relapse mesaure
timeFrame: 12 months
Other outcomes:
Locations:
city: Genova
country: Italy
facility: IRCCS Giannina Gaslini Institute
Study officials:
affiliation: Istituto Giannina Gaslini
name: Gian Marco Ghiggeri, MD
role: STUDY_DIRECTOR
References:
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.
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