<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/NCT03025828</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 16-2402</org_study_id>
    <nct_id>NCT03025828</nct_id>
  </id_info>
  <brief_title>Adrenocorticotropic Hormone in Membranous Nephropathy</brief_title>
  <official_title>Changes in Autoreactive Memory B Cells as Biomarker of Response to Adrenocorticotropic Hormone in Patients With Membranous Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of adrenocorticotropic hormone (ACTH,&#xD;
      Acthar) on the loss of proteins in the urine (proteinuria) in patients with membranous&#xD;
      nephropathy. Acthar is a hormone that stimulates steroid production from small glands above&#xD;
      the kidneys. It has direct protective effects on the kidney and is currently approved by the&#xD;
      FDA to treat kidney disorders associated with proteins in the urine, but the mechanisms of&#xD;
      action are not entirely understood and will be studied in the present trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with membranous nephropathy and nephrotic syndrome will be treated with ACTH for 6&#xD;
      months. Proteinuria remission at 12 months will be the primary endpoint. Different biomarkers&#xD;
      including anti-PLA2R autoantibodies, circulating regulatory T cells, and autoreactive memory&#xD;
      B cells will be serially measured to identify predictors of response to therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2018</start_date>
  <completion_date type="Actual">December 16, 2020</completion_date>
  <primary_completion_date type="Actual">December 16, 2020</primary_completion_date>
  <phase>Phase 4</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 Proteinuria</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complete or Partial Remission</measure>
    <time_frame>12 months</time_frame>
    <description>Complete (proteinuria reduction &lt;500mg/24h) or partial (urinary protein excretion (P/C) &lt;3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Albumin</measure>
    <time_frame>baseline 6 months, 12 months</time_frame>
    <description>Change in serum albumin from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated Glomerular Filtration Rate (GFR)</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>GFR measures kidney function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Anti-PLA2R Memory B Cells</measure>
    <time_frame>12 months</time_frame>
    <description>Number of anti-PLA2R memory B cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-PLA2R Antibodies Levels</measure>
    <time_frame>12 months</time_frame>
    <description>blood levels&#xD;
Number of anti-PLA2R memory B cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>blood levels - one single cell subset identified by different markers</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Membranous Nephropathy</condition>
  <arm_group>
    <arm_group_label>Acthar</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACTHar</intervention_name>
    <description>for 6 months</description>
    <arm_group_label>Acthar</arm_group_label>
    <other_name>ACTH</other_name>
    <other_name>Acthar Injectable Product</other_name>
    <other_name>Repository corticotropin injection</other_name>
    <other_name>RCI</other_name>
    <other_name>Acthar® Gel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 70 years&#xD;
&#xD;
          -  Free of immunosuppression for at least 3 months&#xD;
&#xD;
          -  Capability of understanding the purpose of the study&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Epidermal growth factor receptor (eGFR) &lt; 30ml/min/1.73m2&#xD;
&#xD;
          -  Kidney Transplant&#xD;
&#xD;
          -  Secondary MN (defined on the basis of clinical criteria)&#xD;
&#xD;
          -  Type 1 or Type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus&#xD;
             is not an exclusion)&#xD;
&#xD;
          -  History of previous use of Acthar for treatment of nephrotic syndrome&#xD;
&#xD;
          -  Prior sensitivity to Acthar or other porcine protein products&#xD;
&#xD;
          -  Contraindication to Acthar per Prescribing Information&#xD;
&#xD;
          -  Planned treatment with live or live attenuated vaccines once enrolled in the study&#xD;
&#xD;
          -  More than three previous treatment regiments&#xD;
&#xD;
          -  Participation to other clinical trials over the previous 12 months&#xD;
&#xD;
          -  History of cancer, except carcinoma in situ and treated basal and squamous cell&#xD;
             carcinomas&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Current substance abuse&#xD;
&#xD;
          -  Any clinically relevant condition that might affect study participation and/or study&#xD;
             results&#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>Paolo Cravedi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <results_first_submitted>July 20, 2022</results_first_submitted>
  <results_first_submitted_qc>July 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 15, 2022</results_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Paolo Cravedi</investigator_full_name>
    <investigator_title>Assistant Professor, Nephrology</investigator_title>
  </responsible_party>
  <keyword>Membranous nephropathy</keyword>
  <keyword>adrenocorticotropic hormone</keyword>
  <keyword>ACTH</keyword>
  <keyword>proteinuria</keyword>
  <keyword>glomerulonephritis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Glomerulonephritis, Membranous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenocorticotropic Hormone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>July 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03025828/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment from March 2018 and June 2019</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Acthar</title>
          <description>Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Acthar</title>
          <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
          </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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.75" spread="8.098"/>
                  </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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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>Serum albumin</title>
          <units>g/dL</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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum creatine</title>
          <units>mg/dL</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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.965" spread="0.118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Negative for Anti-PLA2R Ab</title>
          <description>Threshold for anti-PLA2R Ab positivity is 19.9 RU/mL.</description>
          <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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Urine protein/creatinine ratio (P/C)</title>
          <units>g/g</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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.173" spread="3.545"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with previous treatment</title>
          <description>Participants who had previously received treatment with steroids, alkylating agents, calcineurin inhibitors, and/or rituximab.</description>
          <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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Proteinuria</title>
        <description>Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio</description>
        <time_frame>baseline and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Proteinuria</title>
          <description>Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio</description>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.56" lower_limit="4.41" upper_limit="6.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.36" lower_limit="1.1" upper_limit="1.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Complete or Partial Remission</title>
        <description>Complete (proteinuria reduction &lt;500mg/24h) or partial (urinary protein excretion (P/C) &lt;3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete or Partial Remission</title>
          <description>Complete (proteinuria reduction &lt;500mg/24h) or partial (urinary protein excretion (P/C) &lt;3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>complete remission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>partial remission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Albumin</title>
        <description>Change in serum albumin from baseline</description>
        <time_frame>baseline 6 months, 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Albumin</title>
          <description>Change in serum albumin from baseline</description>
          <units>g/dl</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline and 6 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="2.03" upper_limit="3.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>baseline and 12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.65" lower_limit="3.4" upper_limit="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Estimated Glomerular Filtration Rate (GFR)</title>
        <description>GFR measures kidney function.</description>
        <time_frame>baseline and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Estimated Glomerular Filtration Rate (GFR)</title>
          <description>GFR measures kidney function.</description>
          <units>mL/min</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.5" lower_limit="74.74" upper_limit="103.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.5" lower_limit="66.0" upper_limit="101.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Anti-PLA2R Memory B Cells</title>
        <description>Number of anti-PLA2R memory B cells</description>
        <time_frame>12 months</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Anti-PLA2R Memory B Cells</title>
          <description>Number of anti-PLA2R memory B cells</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anti-PLA2R Antibodies Levels</title>
        <description>blood levels&#xD;
Number of anti-PLA2R memory B cells</description>
        <time_frame>12 months</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Anti-PLA2R Antibodies Levels</title>
          <description>blood levels&#xD;
Number of anti-PLA2R memory B cells</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio</title>
        <description>blood levels - one single cell subset identified by different markers</description>
        <time_frame>baseline and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Acthar</title>
            <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio</title>
          <description>blood levels - one single cell subset identified by different markers</description>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" lower_limit="0.03" upper_limit="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" lower_limit="0.08" upper_limit="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Acthar</title>
          <description>Acthar administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly for 6 months of treatment with a cumulative dose exposure of 3,920 units.</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="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </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="4"/>
              </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. Kirk Campbell</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-6271</phone>
      <email>kirk.campbell@mssm.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/NCT03025828
org study id: GCO 16-2402
nct id: NCT03025828
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the effect of adrenocorticotropic hormone (ACTH,
      Acthar) on the loss of proteins in the urine (proteinuria) in patients with membranous
      nephropathy. Acthar is a hormone that stimulates steroid production from small glands above
      the kidneys. It has direct protective effects on the kidney and is currently approved by the
      FDA to treat kidney disorders associated with proteins in the urine, but the mechanisms of
      action are not entirely understood and will be studied in the present trial.
Patients with membranous nephropathy and nephrotic syndrome will be treated with ACTH for 6
      months. Proteinuria remission at 12 months will be the primary endpoint. Different biomarkers
      including anti-PLA2R autoantibodies, circulating regulatory T cells, and autoreactive memory
      B cells will be serially measured to identify predictors of response to therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Proteinuria
time frame: baseline and 12 months
description: Change in proteinuria at baseline versus after 12 months of treatment as measured by urine protein/creatinine ratio
measure: Number of Participants With Complete or Partial Remission
time frame: 12 months
description: Complete (proteinuria reduction <500mg/24h) or partial (urinary protein excretion (P/C) <3.0 g/g (with at least 50% reduction versus baseline) in at least two consecutive visits) remission.
measure: Change in Serum Albumin
time frame: baseline 6 months, 12 months
description: Change in serum albumin from baseline
measure: Estimated Glomerular Filtration Rate (GFR)
time frame: baseline and 12 months
description: GFR measures kidney function.
measure: Number of Anti-PLA2R Memory B Cells
time frame: 12 months
description: Number of anti-PLA2R memory B cells
measure: Anti-PLA2R Antibodies Levels
time frame: 12 months
description: blood levels
Number of anti-PLA2R memory B cells
measure: Change in CD4+CD25+CD127low T Regulatory Cells/CD4+ T Cell Ratio
time frame: baseline and 12 months
description: blood levels - one single cell subset identified by different markers
arm group label: Acthar
arm group type: Experimental
description: Acthar will be administered subcutaneously (SC) 80 units for the first week and then 80 units twice weekly
intervention type: Drug
intervention name: ACTHar
description: for 6 months
arm group label: Acthar
other name: ACTH
other name: Acthar Injectable Product
other name: Repository corticotropin injection
other name: RCI
other name: Acthar® Gel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Paolo Cravedi, MD, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Paolo Cravedi
investigator title: Assistant Professor, Nephrology
mesh term: Kidney Diseases
mesh term: Glomerulonephritis, Membranous
mesh term: Adrenocorticotropic Hormone
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 