Efficacy of Anti-CD20 Antibodies (Rituximab Biosimilar) in the Treatment of Childhood Steroid-dependent Nephrotic Syndrome

Conditions

• Nephrotic Syndrome Steroid-Dependent

Eligibility Criteria

Sex

ALL

Age

3 Years - 24 Years

Healthy Volunteers

Not accepted

Interventions

• Rituximab Biosimilar — DRUG
  for dosage between 100 and 250 mg Rituximab will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg Rituximab will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg Rituximab will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h.
• Mycophenolate Mofetil — DRUG
  1,200 mg/1,73 sqm orally divided in 2 daily doses

Study Details

Anti-CD20 monoclonal antibodies are emerging as the steroid-sparing therapy of choice for nephrotic syndrome. This Randomized Clinical Trial seeks to evaluate whether Rituximab biosimilar maintains drug-free disease remission in patientswith steroid-dependent nephrotic syndrome for 12-24 months and verify its superiority vs. mycophenolate mofetil, the reference standard therapy. The investigators will compare the risk of relapse to test this hypothesis (primary outcome). Secondary objectives will include assessing short- and long-term side-effects and developing specific biomarkers of sensitivity to therapy. Patients will be recruited, treated and followed at IRCCS G Gaslini and IRCCS Bambino Gesù where laboratory studies will be performed at in-site facilities

Key Dates

Start date

Jul 1, 2019

Status verified

Sep 2020

Primary completion

Aug 31, 2020

Completion

Aug 31, 2020

Study Design

Enrollment

30 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Rituximab biosimilar
  * Drug Name: Rituximab biosimilar monoclonal anti-CD20 antibody * Why: Anti-body/antigen interaction results in cell apoptosis and reduced CD20 positive cell related activities (of note CD20 is mostly represented on B cells but also in Th17 cells) * How: RTX IV: for dosage between 100 and 250 mg Rituximab will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg Rituximab will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg Rituximab will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h. * Where: in Hospital * When and how much: once; diluted in 1000 ml of normal saline.
• Active Comparator: Mycophenolate Mofetil
  Drug Name: Mycophenolate Mofetil (MMF) * Why: selective and reversible inhibition of inosine monophosphate dehydrogenase with inhibition that particularly affects lymphocytes since they rely almost exclusively de novo purine synthesis * Procedures: MMF 1,200 mg/1,73 sqm orally divided in 2 daily doses

Primary Outcome Measure

Comparison between RTX and MMF, considering number of partecipants and relative relapses in the two cohorts [ Time Frame: 12-24 months ]