<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/NCT02257697</url>
  </required_header>
  <id_info>
    <org_study_id>HE-69-C-Ne-302</org_study_id>
    <nct_id>NCT02257697</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome</brief_title>
  <official_title>A Multi-center, Randomized, Controlled, Open-label Clinical Study to Evaluate the Efficacy and Safety of Mizoribine in Comparison With Cyclophosphamide in the Treatment of Refractory Nephrotic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asahi Kasei Pharma Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Asahi Kasei Pharma Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To demonstrate that the treatment effect in refractory nephrotic syndrome of MZR is&#xD;
      non-inferior to that of standard therapy CTX through analyzing overall remission rate after&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">November 2018</completion_date>
  <primary_completion_date type="Actual">November 2018</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>Total Remission rate</measure>
    <time_frame>52 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete Remission rate</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial Remission rate</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of Overall Remission rate</measure>
    <time_frame>8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of Complete Remission rate</measure>
    <time_frame>8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of Partial Remission rate</measure>
    <time_frame>8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment failure rate</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes and percentage change of 24 hours urine protein and serum albumin from the baseline</measure>
    <time_frame>8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of and percentage change of SCr, eGFR and BUN from the baseline</measure>
    <time_frame>8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression to End-Stage Renal Disease or Doubling of SCr through the study</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">239</enrollment>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Mizoribine (MZR)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration, daily dose of 150mg (50mg/tablet, t.i.d) All study subjects will receive standard steroid therapies during the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cyclophosphamide (CTX)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous injection with between 0.5 to 1.0 g/m2 body surface area each time (the maximum dose is 1.0 g/day each time).&#xD;
All study subjects will receive standard steroid therapies during the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mizoribine (MZR)</intervention_name>
    <arm_group_label>Mizoribine (MZR)</arm_group_label>
    <other_name>HE-69</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide (CTX)</intervention_name>
    <arm_group_label>Cyclophosphamide (CTX)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who have medical history with clear documentation of diagnosis of nephrotic&#xD;
             syndrome&#xD;
&#xD;
          -  Patient who received renal biopsy within 1 year prior to screening and confirmed the&#xD;
             pathologic classification: Minimal Change Disease (MCD), IgA nephropathy,&#xD;
             Mesangioproliferative Glomerulonephritis (MsPGN), Membranous Nephropathy (MN), Focal&#xD;
             Segmental Glomerulosclerosis (FSGS)&#xD;
&#xD;
          -  Patient with the above different pathologic classification who received adequate&#xD;
             hormone therapy more than 8 weeks (including FSGS more than 12 weeks)prior to&#xD;
             screening and have 24hr-urine protein≥2.0g/day at screening Adequate hormone dose is&#xD;
             defined as prednisone (prednisolone) equivalent dose of 0.8 to 1.0 mg/kg/day&#xD;
             (inclusive)&#xD;
&#xD;
          -  Male or female patient between 18 and 70 years (inclusive) at informed consent&#xD;
             obtained date&#xD;
&#xD;
          -  Patient with body weight between 40kg and 80kg (inclusive) at screening&#xD;
&#xD;
          -  Patients who sign the informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other primary nephrotic syndrome, e.g. membrano-proliferative glomerulonephritis&#xD;
             (MPGN)&#xD;
&#xD;
          -  Secondary nephrotic syndrome (e.g. diabetic nephropathy, anaphylactic purpura&#xD;
             nephritis, lupus nephritis, type B hepatitis-related nephritis, renal amyloidosis)&#xD;
&#xD;
          -  Patient who had history of allergy to any investigational product (MZR, CTX) or&#xD;
             hormone&#xD;
&#xD;
          -  Patient who had received accumulated dosage of CTX &gt;3g within one year prior to&#xD;
             screening&#xD;
&#xD;
          -  Patient who had received immunosuppressant or Chinese traditional medicine with&#xD;
             immunosuppressive effect within 30 days prior to screening&#xD;
&#xD;
          -  Patient who received other investigational drugs within 30 days prior to screening&#xD;
&#xD;
          -  Patient who have received plasma exchange therapy or immunoadsorption therapy within&#xD;
             30 days prior to screening&#xD;
&#xD;
          -  Patient who require pentostatin or live vaccine (not including flu vaccine)&#xD;
&#xD;
          -  Patient who is undergoing renal replacement therapy&#xD;
&#xD;
          -  Patient who received kidney transplantation&#xD;
&#xD;
          -  Patient with malignancy&#xD;
&#xD;
          -  Patient with severe hypertension (SBP &gt; 160mmHg or DBP &gt; 100mmHg) which has not been&#xD;
             effectively controlled&#xD;
&#xD;
          -  Patient with white blood cell count &lt;3×109/L /L(=3.0 GI/L)&#xD;
&#xD;
          -  Patient with SCr &gt; 176.8μmol/L&#xD;
&#xD;
          -  Patient who has a value that is &gt; 3 times of the upper limit of normal range for AST&#xD;
             or ALT&#xD;
&#xD;
          -  Patient with hepatitis B, hepatitis C or HIV infection&#xD;
&#xD;
          -  Patient with other serious infections&#xD;
&#xD;
          -  Patient who is unsuitable for participating in this study in the opinion of&#xD;
             investigators ( e.g. uncontrolled diabetes, central nervous system lupus , lupus&#xD;
             encephalopathy, active psychosis,osteonecrosis of the femoral head, fulminant&#xD;
             hepatitis, peptic ulcer, etc.)&#xD;
&#xD;
          -  Female patient who is pregnant, currently breast feeding or willing to become pregnant&#xD;
&#xD;
          -  Patient with any other diseases that would affect the evaluation of efficacy or safety&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Asahi Kasei Pharma Corporation</last_name>
    <role>Study Chair</role>
    <affiliation>Asahi Kasei Pharma Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Friendship Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Tongren Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China-Japan Friendship Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third Affiliated Hospital of the Third Military Medical University (Daping Hospital)</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fuzhou General Hospital of Nanjing Military Region</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The first Affiliated Hospital of Fujian Medical University</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affiliated Hospital of Guilin Medical University</name>
      <address>
        <city>Guilin</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Guangxi Medical University</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third Hospital of Hebei Medical University</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wuxi People's Hospital</name>
      <address>
        <city>Wuxi</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Nanchang University</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Dalian Medical University</name>
      <address>
        <city>Dalian</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The General Hospital of Shenyang Military Region</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shandong Provincial Hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The General Hospital of Jinan Military Region</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Affilited Hospital of Qingdao University</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renji Hospital Shanghai Jiaotong University School of Medical</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xinhua Hospital Shanghai Jiaotong University School of Medical</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Hospital of Shanxi Medical University</name>
      <address>
        <city>Taiyuan</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Xi'an Jiaotong University</name>
      <address>
        <city>Xian</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kuming General Hospital of Chengdu Military Region</name>
      <address>
        <city>Kunming</city>
        <state>Yunnan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of College of Medicine, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mizoribine</mesh_term>
    <mesh_term>Cyclophosphamide</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/NCT02257697
org study id: HE-69-C-Ne-302
nct id: NCT02257697
lead sponsor: 
has dmc: No
To demonstrate that the treatment effect in refractory nephrotic syndrome of MZR is
      non-inferior to that of standard therapy CTX through analyzing overall remission rate after
      treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total Remission rate
time frame: 52 weeks
measure: Complete Remission rate
time frame: 52 weeks
measure: Partial Remission rate
time frame: 52 weeks
measure: Changes of Overall Remission rate
time frame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of Complete Remission rate
time frame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of Partial Remission rate
time frame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Treatment failure rate
time frame: 52 weeks
measure: Changes and percentage change of 24 hours urine protein and serum albumin from the baseline
time frame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of and percentage change of SCr, eGFR and BUN from the baseline
time frame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Progression to End-Stage Renal Disease or Doubling of SCr through the study
time frame: 52 weeks
arm group label: Mizoribine (MZR)
arm group type: Experimental
description: Oral administration, daily dose of 150mg (50mg/tablet, t.i.d) All study subjects will receive standard steroid therapies during the study.
arm group label: Cyclophosphamide (CTX)
arm group type: Active Comparator
description: Intravenous injection with between 0.5 to 1.0 g/m2 body surface area each time (the maximum dose is 1.0 g/day each time).
All study subjects will receive standard steroid therapies during the study.
intervention type: Drug
intervention name: Mizoribine (MZR)
arm group label: Mizoribine (MZR)
other name: HE-69
intervention type: Drug
intervention name: Cyclophosphamide (CTX)
arm group label: Cyclophosphamide (CTX)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Asahi Kasei Pharma Corporation
role: Study Chair
affiliation: Asahi Kasei Pharma Corporation
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country: China
responsible party type: Sponsor
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Syndrome
mesh term: Mizoribine
mesh term: Cyclophosphamide