Rituximab for Idiopathic Nephrotic Syndrome

Phase 3

Completed

• Conditions: Idiopathic Nephrotic Syndrome
• Interventions: Drug: Rituximab

• Registration Number: NCT04494438
• Lead Sponsor: Istituto Giannina Gaslini

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Study First Submitted: 2020-07-28
• Study First Submitted QC: 2020-07-28
• Study First Posted: 2020-07-31
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-02
• Last Update Posted: 2023-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rituximab	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).

Primary Outcome Measures

Name	Time	Method
Three months proteinuria	3 months	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

Name	Time	Method
Time-to-relapse mesaure	12 months	Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.

Trial Locations

Locations (1)

IRCCS Giannina Gaslini Institute; 🇮🇹 Genova, Italy