Efficacy of humanized anti-CD20 antibodies (Ofatumumab) in the treatment of childhood steroid-dependent nephrotic syndrome and development of cell biomarkers predicting outcome.

INTERVENTION: Trade Name: Arzerra Product Name: ofatumumab Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: OFATUMUMAB CAS Number: 679818‐59‐8 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 20/1‐ Trade Name: Myfenax Pharmaceutical Form: Capsule, hard INN or Proposed INN: MYCOPHENOLATE MOFETIL Other descriptive name: MYCOPHENOLATE MOFETIL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Myfenax Pharmaceutical Form: Tablet INN or Proposed INN: MYCOPHENOLATE MOFETIL Other descriptive name: MYCOPHENOLATE MOFETIL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ CONDITION: steroid dependent nephrotic syndrome ; MedDRA version: 20.0 Level: HLT Classification code 10018365 Term: Glomerulonephritis and nephrotic syndrome System Organ Class: 100000004857 Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: to test whether Ofatumumab is able to achieve and maintain drug‐free disease remission in patients with steroid‐dependent nephrotic syndrome at 12 months. This outcome will be compared to MMF, the drug recommended by Clinical Practice Guidelines (KDIGO) as benchmark of the treatment. The objective of the proposal is therefore to test whether Ofatumumab is superior to MMF in maintaining oral drug‐free disease remission (complete or partial remission) for 12months in patients with SDNS. Primary end point(s): Risk relapse within 12 months without steroid administration Secondary Objective: To reduce the risk of relapse in a longer follow‐up of 24 months in the same group of patients. To verify the occurrence of side‐effects in the short (30 days), mid (90 days) and long‐term periods (2 years).; To analyze B and T cell lymphocyte subsets pre and post‐therapy with Ofatumumab in order to study reconstitution of immune competence in these patients versus patients treated with MMF and to identify biomarkers of response to Ofatumumab and predictors of disease relapse.; ; Timepoint(s) of evaluation of this end point: 12 months SECONDARY OUTCOME: Secondary end point(s): evaluation of circolant cellular popolations as biomarkers or predictors of treatment with anti CD20 Timepoint(s) of evaluation of this end point: 0, 1, 3, 6, 12, 18, 24 months INCLUSION CRITERIA: ‐ Age between 3 and 24 years ‐ Prednison dependent steroid syndrome 0.3‐1mg/Kg/day and receive prednisone for at least six months before enrolment. Steroid dependence is defined by two consecutive relapse during corticosteroid therapy or within 14 days of ceasing therapy. ‐ 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 any time without prejudice to his or her future medical care. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range