Ofatumumab versus Rituximab in treatment of children with steroid and calcineurin inhibitor-dependent idiopatic nephrotic syndrome:

Phase 1

• Conditions: steroid and calcineurin inhibitor-dependent idiopatic nephrotic syndrome; MedDRA version: 21.1Level: PTClassification code 10029164Term: Nephrotic syndromeSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2015-000624-28-IT
• Lead Sponsor: IRCCS ISTITUTO GIANNINA GASLINI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-05
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

-To be in complete disease remission
-Drug dependence: remission has to be maintained with both steroids and CNI
steroid dependence is defined by two consecutive relapses during corticosteroid therapy or within 14 days of ceasing therapy.
CNI (cyclosporine/tacrolimus) dependence is defined by presence of relapse at discontinuation.
-Ability to provide consent and assent: parents’/guardian’s written informed consent, and child’s assent given before any study-related procedure not part of the subject’s normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
-Age between 2 and 18 years

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Positivity to autoimmunity tests (ANA, nDNA, ANCA)
-Reduction of C3 levels.
-eGFR<90/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
-Pregnancy
-Neoplasm
-Infections: previous or actual HBV (with HBeAb positivity) or HCV infection
-CD20 B lymphocytes count <2,5%
-Treatment with Rituximab or cyclophosphamide in the last 6 months
-Homozygous or heterozygous mutations of podocitary genes, commonly involved in the etiology of INS (NPHS1, NPHS2, NPHS3, NPHS6, WT1, COQ2, COQ6, MYO1E, SMARCAL1, LAMB2, SCARB2, CD2AP, TRPC6, ACTN4, INF2, LMX1B, MYH9 )

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: test whether Ofatumumab is superior to Rituximab in maintaining oral drug-free disease remission (complete or partial remission) at 12 months ;Secondary Objective: test whether Ofatumumab is superior to Rituximab in reduce the risk of relapse in a longer follow-up of 24 months in children with steroid and CNI-dependent INS;Primary end point(s): The primary endpoints will be risk of relapse at 12 months without steroid or calcineurin-inhibitors. ;Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary endpoint will be the amount of steroids required to maintain complete disease remission at 6 and 24 months after Ofatumumab or Rituximab pulse.; evaluation of circulating cell populations as<br>biomarkers and predictors of response to treatment with anti-CD20.;Timepoint(s) of evaluation of this end point: 6 months - 24 months ; 6-24 months