<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04494438</url>
  </required_header>
  <id_info>
    <org_study_id>IGG-SN-MAB2 Low Dose</org_study_id>
    <nct_id>NCT04494438</nct_id>
  </id_info>
  <brief_title>Rituximab for Idiopathic Nephrotic Syndrome</brief_title>
  <official_title>Rituximab in Patients With Low Dose Steroid-dependent Idiopathic Nephrotic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Giannina Gaslini</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituto Giannina Gaslini</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open-label, randomized, controlled trial due to value whether the monoclonal antibody&#xD;
      rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS.&#xD;
&#xD;
      The investigators will enroll 30 pediatric patients affected by idiopathic nephrotic&#xD;
      syndrome, who have been in treatment with steroids for at least one year. The lowest dose of&#xD;
      drug required to maintain a stable remission will be between 0.4 and 0.7 mg/ kg/ day.&#xD;
&#xD;
      This trial provides an initial run-in phase of one month during wich remission will be&#xD;
      achieved by means of a standard oral prednisone course. Once remission has been achieved&#xD;
      children will be randomized in a parallel arm open label RCT to continue prednisone alone for&#xD;
      one month (control) or to add a single intravenous infusion of rituximab (375 mg/m2 -&#xD;
      intervention). Prednisone will be tapered in both arms after one month.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2013</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Three months proteinuria</measure>
    <time_frame>3 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time-to-relapse mesaure</measure>
    <time_frame>12 months</time_frame>
    <description>Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Idiopathic Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Steroid tapering.</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <arm_group_label>Rituximab</arm_group_label>
    <other_name>Mabthera</other_name>
    <other_name>Anti CD-20 antibodies</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 1 and 16 years.&#xD;
&#xD;
          -  Steroid-dependent idiopatic nephrotic syndrome for a minimum of 6 to a maximum of 12&#xD;
             months at the time of study entry, regardless of disease duration.&#xD;
&#xD;
          -  Low-dose steroid dependence (between 0.4 and 0.7 mg/ kg/ day)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positivity of autoimmunity tests (ANA, nDNA, ANCA) or reduced C3 levels&#xD;
&#xD;
          -  Histological pattern suggestive for congenital anomalies (diffuse mesangial sclerosis&#xD;
             without IgM deposits, cystic-like tubular dilations, evidence of mithocondrial damage&#xD;
             on electronic microscopy.&#xD;
&#xD;
          -  Histological pattern not correlated with idiopathic nephrotic syndrome in the&#xD;
             pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or&#xD;
             localized vasculitis, amyloidosis).&#xD;
&#xD;
          -  Evidence of homozygous or heterozygous mutations in podocitary genes commonly involved&#xD;
             in the pathology (NPHS1, NPHS2, WT1).&#xD;
&#xD;
          -  Estimated glomerula filtration rate (eGFR) &lt; 60ml/min.&#xD;
&#xD;
          -  Presence of circulating IgM against HCV, HBV, parvovirus or mycoplasm.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gian Marco Ghiggeri, MD</last_name>
    <role>Study Director</role>
    <affiliation>Istituto Giannina Gaslini</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS Giannina Gaslini Institute</name>
      <address>
        <city>Genova</city>
        <zip>16147</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, Ghio L, Merscher-Gomez S, Edefonti A, Pasini A, Montini G, Murtas C, Wang X, Muruve D, Vaglio A, Martorana D, Pani A, Scolari F, Reiser J, Ghiggeri GM. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013 Nov;84(5):1025-33. doi: 10.1038/ki.2013.211. Epub 2013 Jun 5.</citation>
    <PMID>23739238</PMID>
  </reference>
  <reference>
    <citation>Ghiggeri GM, Musante L, Candiano G, Bruschi M, Santucci L, Barbano G, Trivelli A, Rivabella L, Gusmano R, Perfumo F. Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis. Pediatr Nephrol. 2007 Nov;22(11):1953-6. doi: 10.1007/s00467-007-0550-y. Epub 2007 Jul 28.</citation>
    <PMID>17661091</PMID>
  </reference>
  <reference>
    <citation>Pescovitz MD, Book BK, Sidner RA. Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med. 2006 May 4;354(18):1961-3. doi: 10.1056/NEJMc055495. No abstract available.</citation>
    <PMID>16672715</PMID>
  </reference>
  <reference>
    <citation>Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, Benetti E, Murtas C, Messina G, Massella L, Porcellini MG, Montagna M, Regazzi M, Scolari F, Ghiggeri GM. Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol. 2012 Jun;23(6):1117-24. doi: 10.1681/ASN.2011080775. Epub 2012 May 10.</citation>
    <PMID>22581994</PMID>
  </reference>
  <reference>
    <citation>Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011 Jun;6(6):1308-15. doi: 10.2215/CJN.09421010. Epub 2011 May 12.</citation>
    <PMID>21566104</PMID>
  </reference>
  <reference>
    <citation>Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.</citation>
    <PMID>24480824</PMID>
  </reference>
  <reference>
    <citation>Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008 Aug;23(8):1269-79. doi: 10.1007/s00467-008-0814-1. Epub 2008 May 9.</citation>
    <PMID>18465150</PMID>
  </reference>
  <reference>
    <citation>Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N, Egido J, Praga M; Trabajo de Enfermedades Glomerulares de la Sociedad Espanola de Nefrologia (GLOSEN). Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009 Aug;4(8):1317-23. doi: 10.2215/CJN.00570109. Epub 2009 Jul 2.</citation>
    <PMID>19578004</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>January 2, 2023</last_update_submitted>
  <last_update_submitted_qc>January 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Istituto Giannina Gaslini</investigator_affiliation>
    <investigator_full_name>Gian Marco Ghiggeri MD, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Nephrotic syndrome</keyword>
  <keyword>Proteinuria</keyword>
  <keyword>Rituximab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Nephrosis, Lipoid</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04494438
org study id: IGG-SN-MAB2 Low Dose
nct id: NCT04494438
lead sponsor: 
has dmc: Yes
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Three months proteinuria
time frame: 3 months
description: 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.
measure: Time-to-relapse mesaure
time frame: 12 months
description: Risk of relapse of proteinuria and need for recovery of steroids, with survival analysis after withdrawal of steroids.
arm group label: Steroid tapering.
arm group type: No Intervention
arm group label: Rituximab
arm group type: Experimental
description: 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).
intervention type: Drug
intervention name: Rituximab
arm group label: Rituximab
other name: Mabthera
other name: Anti CD-20 antibodies
criteria: 
gender: All
minimum age: 1 Year
maximum age: 16 Years
healthy volunteers: No
last name: Gian Marco Ghiggeri, MD
role: Study Director
affiliation: Istituto Giannina Gaslini
facility: 
country: Italy
citation: Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, Ghio L, Merscher-Gomez S, Edefonti A, Pasini A, Montini G, Murtas C, Wang X, Muruve D, Vaglio A, Martorana D, Pani A, Scolari F, Reiser J, Ghiggeri GM. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013 Nov;84(5):1025-33. doi: 10.1038/ki.2013.211. Epub 2013 Jun 5.
PMID: 23739238
citation: Ghiggeri GM, Musante L, Candiano G, Bruschi M, Santucci L, Barbano G, Trivelli A, Rivabella L, Gusmano R, Perfumo F. Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis. Pediatr Nephrol. 2007 Nov;22(11):1953-6. doi: 10.1007/s00467-007-0550-y. Epub 2007 Jul 28.
PMID: 17661091
citation: Pescovitz MD, Book BK, Sidner RA. Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med. 2006 May 4;354(18):1961-3. doi: 10.1056/NEJMc055495. No abstract available.
PMID: 16672715
citation: Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, Benetti E, Murtas C, Messina G, Massella L, Porcellini MG, Montagna M, Regazzi M, Scolari F, Ghiggeri GM. Rituximab in children with resistant idiopathic nephrotic syndrome. J Am Soc Nephrol. 2012 Jun;23(6):1117-24. doi: 10.1681/ASN.2011080775. Epub 2012 May 10.
PMID: 22581994
citation: Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011 Jun;6(6):1308-15. doi: 10.2215/CJN.09421010. Epub 2011 May 12.
PMID: 21566104
citation: Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.
PMID: 24480824
citation: Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008 Aug;23(8):1269-79. doi: 10.1007/s00467-008-0814-1. Epub 2008 May 9.
PMID: 18465150
citation: Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N, Egido J, Praga M; Trabajo de Enfermedades Glomerulares de la Sociedad Espanola de Nefrologia (GLOSEN). Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009 Aug;4(8):1317-23. doi: 10.2215/CJN.00570109. Epub 2009 Jul 2.
PMID: 19578004
responsible party type: Principal Investigator
investigator affiliation: Istituto Giannina Gaslini
investigator full name: Gian Marco Ghiggeri MD, PhD
investigator title: Principal Investigator
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Nephrosis, Lipoid
mesh term: Syndrome
mesh term: Rituximab