<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/NCT02197767</url>
  </required_header>
  <id_info>
    <org_study_id>13-006694</org_study_id>
    <nct_id>NCT02197767</nct_id>
  </id_info>
  <brief_title>Pilot Study of Rituximab to Treat Fibrillary Glomerulonephritis</brief_title>
  <official_title>A Single Center Pilot Trial of Rituximab in the Treatment of Fibrillary Glomerulonephritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot study is being done to see if the study medication, Rituximab, preserves kidney&#xD;
      function after 12 months of taking the drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase II, open-label pilot study to determine if the use of Rituximab reduces&#xD;
      proteinuria over a 12 month period and is there preservation of kidney function with the use&#xD;
      of this study drug. Each patient will be treated with 2 intravenous infusions of rituximab&#xD;
      1000 mg, two weeks apart for a total of 2 doses. Each patient will be retreated with&#xD;
      identical 2 intravenous infusions of rituximab, two weeks apart at 6 months after the first&#xD;
      infusion, irrespective of cluster of differentiation (CD) 20+ cell counts. Thus, each&#xD;
      participant will receive 4 infusions of rituximab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">April 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in 24 Hour Creatinine Clearance</measure>
    <time_frame>Day 0, Day 365</time_frame>
    <description>Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Proteinuria</measure>
    <time_frame>Day 0, Day 365</time_frame>
    <description>Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Fibrillary Glomerulonephritis</condition>
  <arm_group>
    <arm_group_label>rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rituximab</intervention_name>
    <description>1000 mg infusion</description>
    <arm_group_label>rituximab</arm_group_label>
    <other_name>Rituxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fibrillary Glomerulonephritis with diagnostic biopsy performed within the last 2 years&#xD;
&#xD;
          -  Proteinuria &gt;1 gram&#xD;
&#xD;
          -  Age &gt; 18 years but &lt; 80 years&#xD;
&#xD;
          -  Adequately controlled blood pressure (BP&lt;140/90 mmHg in &gt;75% of the readings) for at&#xD;
             least 3 months prior to enrollment with the use of (angiotensin converting enzyme&#xD;
             inhibitors (ACEi) and/or angiotensin-receptor blockers (ARB), if tolerated.&#xD;
&#xD;
          -  Women must be post- menopausal, surgically sterile or practicing a medically approved&#xD;
             method of contraception&#xD;
&#xD;
          -  Able and willing to give written informed consent and comply with the requirements of&#xD;
             the study protocol&#xD;
&#xD;
          -  Adequate renal function as indicated by estimated glomerular filtration rate (GFR) &gt;&#xD;
             25 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD/EPI)&#xD;
             formula or a quantified creatinine clearance &gt;25 mL/min, and/or serum creatinine &lt;3.0&#xD;
             mg/dL in the presence of ACEi/ARB therapy&#xD;
&#xD;
          -  Adequate bone marrow function, as indicated by hemoglobin &gt;7.0 gm/dL, white count &gt;3.0&#xD;
             x 10(9), platelet count &gt;100 x 10(9)&#xD;
&#xD;
          -  Negative chest x-ray within one year&#xD;
&#xD;
          -  Negative serum pregnancy test (for women of child bearing age)&#xD;
&#xD;
          -  Normal organ function.&#xD;
&#xD;
          -  Subject agrees to use an acceptable method of birth control during treatment and for&#xD;
             twelve months after completion of treatment&#xD;
&#xD;
          -  Subject has provided written informed consent&#xD;
&#xD;
          -  Subject agrees to discontinue routine use of non-steroidal anti-inflammatory drugs&#xD;
&#xD;
          -  Absolute Neutrophil Count (ANC): &gt; 1000/ mm3&#xD;
&#xD;
          -  Adequate liver function, as indicated by aspartate aminotransferase (AST), alanine&#xD;
             aminotransferase (ALT), alkaline phosphatase and total bilirubin &lt; 2x upper limit or&#xD;
             normal unless related to primary disease&#xD;
&#xD;
          -  Negative HBsAg and anti-hepatitis B (HBc) lab values within 1 year of signing consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy (determined by a serum pregnancy test for all women of childbearing&#xD;
             potential within 7 days of treatment), or lactating.&#xD;
&#xD;
          -  Inability to comply with study and/or follow-up procedures&#xD;
&#xD;
          -  History of HIV (a documented positive lab value within one year of enrollment)&#xD;
&#xD;
          -  Presence of active infection&#xD;
&#xD;
          -  New York Heart Association Classification III or IV heart disease&#xD;
&#xD;
          -  Concomitant malignancies or previous malignancies within the last five years, with the&#xD;
             exception of adequately treated basal or squamous cell carcinoma of the skin or&#xD;
             carcinoma in situ of the cervix&#xD;
&#xD;
          -  History of psychiatric disorder&#xD;
&#xD;
          -  At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to&#xD;
             randomization&#xD;
&#xD;
          -  At the Investigator's discretion, positive Hepatitis C serology&#xD;
&#xD;
          -  Known history of diabetes mellitus or a Hemoglobin A1c result &gt; 6.0% within 90 days&#xD;
             prior to enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen B. Erickson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <results_first_submitted>January 16, 2019</results_first_submitted>
  <results_first_submitted_qc>January 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 6, 2019</results_first_posted>
  <last_update_submitted>January 16, 2019</last_update_submitted>
  <last_update_submitted_qc>January 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Stephen B. Erickson, M.D.</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>fibrillary glomerulonephritis</keyword>
  <keyword>rituximab</keyword>
  <keyword>Rituxan</keyword>
  <keyword>MabThera</keyword>
  <keyword>Zytux™</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glomerulonephritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 7, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT02197767/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Rituximab</title>
          <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.&#xD;
rituximab: 1000 mg infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Rituximab</title>
          <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.&#xD;
rituximab: 1000 mg infusion</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.5" spread="2.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in 24 Hour Creatinine Clearance</title>
        <description>Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).</description>
        <time_frame>Day 0, Day 365</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rituximab</title>
            <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.&#xD;
rituximab: 1000 mg infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in 24 Hour Creatinine Clearance</title>
          <description>Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).</description>
          <units>mL/min/SA</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.0" spread="15.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.072</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Proteinuria</title>
        <description>Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.</description>
        <time_frame>Day 0, Day 365</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rituximab</title>
            <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.&#xD;
rituximab: 1000 mg infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Proteinuria</title>
          <description>Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.</description>
          <units>mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2589.8" spread="1741.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.068</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for the duration of the study until 30 days following the last administration of study treatment or study discontinuation/termination, whichever was earlier.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Rituximab</title>
          <description>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.&#xD;
rituximab: 1000 mg infusion</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Stephen B. Erickson</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-284-4083</phone>
      <email>Erickson.Stephen@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02197767
org study id: 13-006694
nct id: NCT02197767
lead sponsor: 
collaborator: 
has dmc: No
This pilot study is being done to see if the study medication, Rituximab, preserves kidney
      function after 12 months of taking the drug.
This is a Phase II, open-label pilot study to determine if the use of Rituximab reduces
      proteinuria over a 12 month period and is there preservation of kidney function with the use
      of this study drug. Each patient will be treated with 2 intravenous infusions of rituximab
      1000 mg, two weeks apart for a total of 2 doses. Each patient will be retreated with
      identical 2 intravenous infusions of rituximab, two weeks apart at 6 months after the first
      infusion, irrespective of cluster of differentiation (CD) 20+ cell counts. Thus, each
      participant will receive 4 infusions of rituximab.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in 24 Hour Creatinine Clearance
time frame: Day 0, Day 365
description: Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).
measure: Change in Proteinuria
time frame: Day 0, Day 365
description: Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.
arm group label: rituximab
arm group type: Experimental
description: rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.
intervention type: Drug
intervention name: rituximab
description: 1000 mg infusion
arm group label: rituximab
other name: Rituxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Stephen B. Erickson, M.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Stephen B. Erickson, M.D.
investigator title: PI
mesh term: Glomerulonephritis
mesh term: Rituximab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 