Rituximab Versus Mycophenolate Mofetil in Children With Steroid-dependent Idiopathic Nephrotic Syndrome.

NCT04585152 | Unknown Phase 2 DMC

• 1 other identifier: RTXvsMMF
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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 patients with steroid-dependent nephrotic syndrome for 12-24 months and verify its superiority vs. mycophenolate mofetil (1,200 mg/m2 orally in 2 daily doses). 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.

Conditions

Nephrotic Syndrome Steroid-Dependent

Keywords

nephrotic syndrome treatment; rituximab; Mycophenolate Mofetil

Outcome Measures

Primary Outcomes (1)

• Comparison between RTX and MMF, considering remission intervals (in months) in the two cohorts

  Comparison between RTX and MMF to maintain remission of NS for 12-24 months in children with primary SDNS. All the participats (n=160) will document their proteinuria and their urine will be analyzed periodically (at least every three months); relapse is defined by uPCR ≥2000 mg/g (≥ 200 mg/mmol) or \> 3+ protein on urine dipstick for 3 consecutive days (KDIGO Clinical Practice Guideline for Glomerulonephritis, Kidney International Supplement, 2012 2, 163-171) and complete remission is defined by uPCR \<200 mg/g (\<20 mg/mmol) or o1+ of protein on urine dipstick for 3 consecutive days (KDIGO Clinical Practice Guideline for Glomerulonephritis, Kidney International Supplement, 2012 2, 163-171).

  12-24 months

Secondary Outcomes (1)

• RTX safety by evaluation and documentation of side effects measuring frequency and severity of any treatment-related adverse events as assessed by CTCAE v4.0

  36 months

Other Outcomes (1)

• Biomarkers of immune competence: mononuclear cells (PBMCs) by cytometry, serum immunoglobulin

  36 months

Study Arms (2)

Rituximab biosimilar

EXPERIMENTAL

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.

Drug: Rituximab Biosimilar

Mycophenolate mofetil

ACTIVE COMPARATOR

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/m2 orally divided in 2 daily doses

Drug: Rituximab Biosimilar

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; Rituximab biosimilar

Eligibility Criteria

• Age: 3 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 in the last 6 months

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead
• Bambino Gesù Hospital and Research Institute: collaborator

Study Sites (1)

IRCCS G. Gaslini

Genova, 16148, Italy

RECRUITING

Related Publications (2)

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

• Lugani F, Angeletti A, Ravani P, Vivarelli M, Colucci M, Caridi G, Verrina E, Emma F, Ghiggeri GM. Randomised controlled trial comparing rituximab to mycophenolate mofetil in children and young adults with steroid-dependent idiopathic nephrotic syndrome: study protocol. BMJ Open. 2021 Nov 29;11(11):e052450. doi: 10.1136/bmjopen-2021-052450.

  PMID: 34845071 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• GianMarco Ghiggeri, MD

  Istituto Giannina Gaslini

  PRINCIPAL INVESTIGATOR

Central Study Contacts

GianMarco Ghiggeri, MD

CONTACT

+39 010 56363523; gmarcoghiggeri@gaslini.org

Francesca Lugani, MD, PhD

CONTACT

+39 010 56363523; francescalugani@gaslini.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, director of Nephrology, Dialysis and Transplantation Unit

Model Details: The RTX-MMF trial is an open-label, two-parallel-arm, controlled and randomized clinical trial testing the superiority of RTX over MMF in maintaining steroid free disease remission in patients with SDNS

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 14, 2020
• Study Start: October 15, 2020
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: it will be public on peer reviewed journal
• Access Criteria: it will be public on peer reviewed journal

Locations

IT (1)