<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/NCT01673295</url>
  </required_header>
  <id_info>
    <org_study_id>P1200_11</org_study_id>
    <nct_id>NCT01673295</nct_id>
  </id_info>
  <brief_title>RING - Rituximab for Lupus Nephritis With Remission as a Goal</brief_title>
  <acronym>RING</acronym>
  <official_title>RING - Rituximab for Lupus Nephritis With Remission as a Goal, an Investigator-initiated Randomized International Open Multicentric Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Frédéric A. Houssiau, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Université Catholique de Louvain</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      OBJECTIVE To test whether Rituximab (RTX) is efficacious to achieve complete renal response&#xD;
      (CR) in Lupus Nephritis (LN) patients with persistent proteinuria (≥1g/d) despite at least 6&#xD;
      months of standard of care (SOC).&#xD;
&#xD;
      STUDY DESIGN Investigator-initiated randomized international open multicentric 104-week&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After screening (week -8), patients enter in a run-in period of 6 weeks during which&#xD;
      treatment is unchanged. At week -2, if persistent proteinuria is confirmed (uP/C ratio ≥1&#xD;
      expressed in mg/mg), patients will be randomized in a 1/1 ratio to 1 of 2 treatment groups as&#xD;
      follows :&#xD;
&#xD;
      RTX group Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.Control group&#xD;
      Subjects will not receive RTX infusions. In both arms, azathioprine (AZA) or mycophenolate&#xD;
      mofetil (MMF) will be continued. If prescribed, prednisolone dose should not be &gt; 10 mg/day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <completion_date type="Anticipated">November 2016</completion_date>
  <primary_completion_date type="Anticipated">November 2015</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>The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104.</measure>
    <time_frame>104 weeks</time_frame>
    <description>CR is defined as :&#xD;
uP/C ratio ≤0.5 (expressed in mg/mg) measured in a 24-h urine collection; and&#xD;
eGFR &gt;=60ml/min or, if &lt;60ml/min at screening, not fallen by &gt;20% compared to screening; and&#xD;
no increase of glucocorticoïds (GC) throughout the study (except for two limited courses as per protocol; vide infra); and&#xD;
no introduction of another immunosuppressant.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">194</enrollment>
  <condition>Lupus Nephritis</condition>
  <arm_group>
    <arm_group_label>RTX group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will not receive RTX infusions and will be followed in standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RTX infusions</intervention_name>
    <description>RTX + Standard of Care</description>
    <arm_group_label>RTX group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of Care only</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All the following inclusion criteria are to be met :&#xD;
&#xD;
          1. SLE, according to ACR and/or SLICC (Arthritis Rheum 2012; May 2; doi:&#xD;
             10.1002/art.34473) criteria ;&#xD;
&#xD;
          2. Age ≥15y (except if local ethics committee imposes ≥18y) ;&#xD;
&#xD;
          3. ISN/RPS 2003 Class III (A or A/C), IV (A or A/C ; S or G) or V lupus GN confirmed on&#xD;
             renal biopsy performed within 24 months before screening ;&#xD;
&#xD;
          4. Having received one out of four following immunosuppressive regimens:&#xD;
&#xD;
             i): Euro-Lupus (EL) intravenous (IV) cyclophosphamide (CY) (6x 500 mg q2w) followed by&#xD;
             AZA/MMF for 3 months ; ii): NIH IVCY for 6M (6 monthly pulses) followed by AZA/MMF for&#xD;
             3 months ; iii): MMF for at least 6 months at a dose of 2g/day (or the maximal&#xD;
             tolerated dose; iv): AZA for at least 6 months at a dose of 2 mg/kg/day (or the&#xD;
             maximal toerated dose).&#xD;
&#xD;
             All patients should be on AZA or MMF at screening. In all regimens, MMF can be&#xD;
             replaced by enteric-coated mycophenolic acid (eMPA) ;&#xD;
&#xD;
          5. If on GC, being on maximum 10 mg equivalent prednisolone/d at screening (for at least&#xD;
             2 weeks) ;&#xD;
&#xD;
          6. uP/C ratio ≥1 (expressed in mg/mg) measured in a 24-h urine collection, confirmed at&#xD;
             randomization (w-2) ;&#xD;
&#xD;
          7. Contraception (any type ; sexual abstinence is an alternative to contraception in&#xD;
             paediatric patients) ;&#xD;
&#xD;
          8. Signed informed consent (drafted according to local practice and approved by the local&#xD;
             ethics committee).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Any of the following :&#xD;
&#xD;
          1. Recent or ongoing renal flare defined as either i) : fall in estimated glomerular&#xD;
             filtration rate (eGFR ; MDRD) ≥25% within 3 month prior to screening or between&#xD;
             screening and randomization ; or ii) : increase in urine protein by ≥100% to &gt;3.5g/d&#xD;
             compared to previous assessment ;&#xD;
&#xD;
          2. 24-h proteinuria decline &gt;50% over previous 6 months ;&#xD;
&#xD;
          3. Treatment with ≥10 mg equivalent prednisolone/d in the last 2 weeks before screening ;&#xD;
&#xD;
          4. Pregnancy or breast-feeding ;&#xD;
&#xD;
          5. Anticipated non-compliance with the protocol ;&#xD;
&#xD;
          6. History of malignancy (except non-melanoma skin and cervical intraepithelial cancer) ;&#xD;
&#xD;
          7. Previous treatment with RTX (whenever) and previous treatment with another biologic&#xD;
             agent within the last 6 months ;&#xD;
&#xD;
          8. HIV infection ;&#xD;
&#xD;
          9. Active HBV/HCV/TB infection ;&#xD;
&#xD;
         10. Severe liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,&#xD;
             haematologic or psychiatric disturbances, that would contraindicate inclusion in the&#xD;
             protocol, as judged by the clinician.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frédéric A Houssiau, MD PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cliniques universitaires Saint-Luc</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Frédéric A Houssiau, MD PHD</last_name>
    <phone>+32 2 7645391</phone>
    <email>frederic.houssiau@uclouvain.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Geneviève J Depresseux, Trial Coord</last_name>
    <phone>+32 2 7645395</phone>
    <email>genevieve.depresseux@uclouvain.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frédéric A Houssiau, MD PHD</last_name>
      <phone>+32 2 7645391</phone>
      <email>frederic.houssiau@uclouvain.be</email>
    </contact>
    <contact_backup>
      <last_name>Geneviève J Depresseux, Trial Coord</last_name>
      <phone>+32 2 7645395</phone>
      <email>genevieve.depresseux@uclouvain.be</email>
    </contact_backup>
    <investigator>
      <last_name>Frédéric A Houssiau, MD PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>May 27, 2015</last_update_submitted>
  <last_update_submitted_qc>May 27, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 28, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Université Catholique de Louvain</investigator_affiliation>
    <investigator_full_name>Frédéric A. Houssiau, MD, PhD</investigator_full_name>
    <investigator_title>Professeur Ordinaire, Chef de Service Clinique</investigator_title>
  </responsible_party>
  <keyword>Lupus Nephritis</keyword>
  <keyword>Rituximab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephritis</mesh_term>
    <mesh_term>Lupus Nephritis</mesh_term>
  </condition_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/NCT01673295
org study id: P1200_11
nct id: NCT01673295
lead sponsor: 
has dmc: Yes
OBJECTIVE To test whether Rituximab (RTX) is efficacious to achieve complete renal response
      (CR) in Lupus Nephritis (LN) patients with persistent proteinuria (≥1g/d) despite at least 6
      months of standard of care (SOC).

      STUDY DESIGN Investigator-initiated randomized international open multicentric 104-week
      study.
After screening (week -8), patients enter in a run-in period of 6 weeks during which
      treatment is unchanged. At week -2, if persistent proteinuria is confirmed (uP/C ratio ≥1
      expressed in mg/mg), patients will be randomized in a 1/1 ratio to 1 of 2 treatment groups as
      follows :

      RTX group Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.Control group
      Subjects will not receive RTX infusions. In both arms, azathioprine (AZA) or mycophenolate
      mofetil (MMF) will be continued. If prescribed, prednisolone dose should not be > 10 mg/day.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104.
time frame: 104 weeks
description: CR is defined as :
uP/C ratio ≤0.5 (expressed in mg/mg) measured in a 24-h urine collection; and
eGFR >=60ml/min or, if <60ml/min at screening, not fallen by >20% compared to screening; and
no increase of glucocorticoïds (GC) throughout the study (except for two limited courses as per protocol; vide infra); and
no introduction of another immunosuppressant.
arm group label: RTX group
arm group type: Experimental
description: Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.
arm group label: Control group
arm group type: Active Comparator
description: Subjects will not receive RTX infusions and will be followed in standard of care
intervention type: Drug
intervention name: RTX infusions
description: RTX + Standard of Care
arm group label: RTX group
intervention type: Other
intervention name: Standard of Care
description: Standard of Care only
arm group label: Control group
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: No
last name: Frédéric A Houssiau, MD PHD
role: Principal Investigator
affiliation: Cliniques universitaires Saint-Luc
last name: Frédéric A Houssiau, MD PHD
phone: +32 2 7645391
email: frederic.houssiau@uclouvain.be
last name: Geneviève J Depresseux, Trial Coord
phone: +32 2 7645395
email: genevieve.depresseux@uclouvain.be
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Belgium
responsible party type: Sponsor-Investigator
investigator affiliation: Université Catholique de Louvain
investigator full name: Frédéric A. Houssiau, MD, PhD
investigator title: Professeur Ordinaire, Chef de Service Clinique
mesh term: Nephritis
mesh term: Lupus Nephritis