<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/NCT04410198</url>
  </required_header>
  <id_info>
    <org_study_id>FGCL-4592-097</org_study_id>
    <nct_id>NCT04410198</nct_id>
  </id_info>
  <brief_title>Study of Roxadustat Conversion in Participants Receiving Stable Erythropoiesis-Stimulating Agent (ESA) or as Initial Anemia Treatment in Chronic Dialysis Participants</brief_title>
  <official_title>A Phase 3b Multicenter, Open-Label Single Arm Study of Roxadustat: Either as Conversion From a Continuous Erythropoietin Receptor Activator (CERA), or as Initial Anemia Treatment in Hemodialysis (HD) Patients - DENALI Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>FibroGen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>FibroGen</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 assess the safety and effectiveness of Roxadustat dosing&#xD;
      regimens among chronic dialysis participants converted from ESA therapy or who are ESA-naïve.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 26, 2020</start_date>
  <completion_date type="Actual">October 11, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <phase>Phase 3</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>Percentage of Participants With Mean Hb Value ≥10 g/dL</measure>
    <time_frame>Week 16 through Week 24</time_frame>
    <description>Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Hb Change From Baseline to Average Hb From Weeks 16-24</measure>
    <time_frame>Baseline, Weeks 16-24</time_frame>
    <description>Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">203</enrollment>
  <condition>Anemia Associated With End Stage Renal Disease (ESRD)</condition>
  <arm_group>
    <arm_group_label>Roxadustat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant requires roxadustat &lt;60 milligrams (mg)/week to maintain Hb levels, the dose frequency will be reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose will be based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose will be based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations will be made every 4 weeks and doses will be titrated based on Hb level and rate of Hb change. The prescribed dose will not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever is lower.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Roxadustat</intervention_name>
    <description>Roxadustat will be administered per dose and schedule specified in the arm description.</description>
    <arm_group_label>Roxadustat</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Receiving chronic dialysis for end stage renal disease (ESRD)&#xD;
&#xD;
          -  Vascular access must be a functioning native arteriovenous fistula or graft with&#xD;
             adequate flow in the opinion of the investigator, or permanent tunneled catheter&#xD;
&#xD;
          -  Screening hemoglobin criteria (based on central lab value; measured within 10 days&#xD;
             prior to initiating Roxadustat treatment: Participants converting from CERA: screening&#xD;
             heamoglobin was between 9.0 to 12.0 g/dL; Participants initiating anemia treatment:&#xD;
             &lt;10.0 g/dL&#xD;
&#xD;
          -  Ferritin ≥ 50 nanograms (ng)/milliliter (mL), Transferrin saturation (TSAT) ≥ 10% at&#xD;
             screening&#xD;
&#xD;
          -  Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are&#xD;
             ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN at screening&#xD;
             and prior to initiating roxadustat treatment.&#xD;
&#xD;
          -  Body weight between 45.0 to 160.0 kg&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Red blood cell (RBC) transfusion within 4 weeks prior to enrollment&#xD;
&#xD;
          -  Known history of myelodysplastic syndrome or multiple myeloma&#xD;
&#xD;
          -  Known hereditary hematologic disease or other known causes for anemia other than&#xD;
             chronic kidney disease (CKD)&#xD;
&#xD;
          -  Known chronic inflammatory disease that is determined by the investigator to be the&#xD;
             primary cause of anemia&#xD;
&#xD;
          -  Active or chronic gastrointestinal bleeding&#xD;
&#xD;
          -  Treated with iron-chelating agents within 4 weeks prior to enrollment&#xD;
&#xD;
          -  History of New York Heart Association (NYHA) Class III or IV congestive heart failure&#xD;
&#xD;
          -  History of myocardial infarction (MI), acute coronary syndrome, stroke, seizure, or a&#xD;
             thrombotic/thromboembolic event (excluding vascular dialysis access&#xD;
             stenosis/thrombosis) within 12 weeks prior to enrollment&#xD;
&#xD;
          -  Uncontrolled hypertension, in the opinion of the Investigator&#xD;
&#xD;
          -  Diagnosis or suspicion of renal cell carcinoma as shown on renal imaging performed&#xD;
             within 24 weeks prior to enrollment&#xD;
&#xD;
          -  History of malignancy, except for cancers determined to be cured or in remission for&#xD;
             ≥2 years, curatively resected basal cell or squamous cell skin cancers, cervical&#xD;
             cancer in situ, or resected colonic polyps&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Eisner</last_name>
    <role>Study Chair</role>
    <affiliation>FibroGen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Caldwell</city>
        <state>Idaho</state>
        <zip>83642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Tupelo</city>
        <state>Mississippi</state>
        <zip>38801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Saint Ann</city>
        <state>Missouri</state>
        <zip>63074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <zip>77479</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Saint George</city>
        <state>Utah</state>
        <zip>84790</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <results_first_submitted>June 24, 2022</results_first_submitted>
  <results_first_submitted_qc>August 19, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 13, 2022</results_first_posted>
  <last_update_submitted>August 19, 2022</last_update_submitted>
  <last_update_submitted_qc>August 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2022</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>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Anemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT04410198/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 9, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT04410198/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Roxadustat</title>
          <description>Participants received roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant required roxadustat &lt;60 milligrams (mg)/week to maintain hemoglobin (Hb) levels, the dose frequency was reduced in a stepwise manner, for example, to twice weekly (BIW), and then once weekly (QW). For participants converted from continuous erythropoietin receptor activator (CERA), the initial roxadustat dose was based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever was lower.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="203"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="203"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="201"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="166"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Transferred/Relocation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Kidney Transplant</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set included all enrolled participants who received at least 1 dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Roxadustat</title>
          <description>Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat &lt;60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose was based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="203"/>
          </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="203"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.7" spread="14.13"/>
                  </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="203"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="203"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="168"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="203"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="105"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Hb</title>
          <population>Here, Number analyzed = Participants evaluable for this baseline measure.</population>
          <units>grams (g)/deciliter (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="202"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.402" spread="0.8159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Mean Hb Value ≥10 g/dL</title>
        <description>Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.</description>
        <time_frame>Week 16 through Week 24</time_frame>
        <population>The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Roxadustat</title>
            <description>Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat &lt;60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose was based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Mean Hb Value ≥10 g/dL</title>
          <description>Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.</description>
          <population>The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.7" lower_limit="79.1" upper_limit="90.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Hb Change From Baseline to Average Hb From Weeks 16-24</title>
        <description>Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.</description>
        <time_frame>Baseline, Weeks 16-24</time_frame>
        <population>The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Roxadustat</title>
            <description>Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat &lt;60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose was based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Hb Change From Baseline to Average Hb From Weeks 16-24</title>
          <description>Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.</description>
          <population>The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.</population>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="1.007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to 28 days post last dose of roxadustat (Week 28)</time_frame>
      <desc>The safety analysis set included all enrolled participants who received at least 1 dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Roxadustat</title>
          <description>Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat &lt;60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose was based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with &lt;6 weeks of prior CERA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="52" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vitritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Intestinal perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pancreatic pseudocyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pancreatitis relapsing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Catheter site haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hypothermia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Medical device site haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Arteriovenous graft site infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Coronavirus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Endophthalmitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Gangrene</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Oesophageal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Staphylococcal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arteriovenous fistula aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Arteriovenous fistula occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Arteriovenous fistula site complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Vascular access malfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Vascular access steal syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hyperammonaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Brain injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Neurotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Post cardiac arrest syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Spinal cord infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Status epilepticus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device malfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Bipolar disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hypertensive emergency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
              <event>
                <sub_title>Hypertensive urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="203"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Information Desk</name_or_title>
      <organization>FibroGen, Inc.</organization>
      <phone>415-978-1441</phone>
      <email>FG4592-097Study@fibrogen.com</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/NCT04410198
org study id: FGCL-4592-097
nct id: NCT04410198
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the safety and effectiveness of Roxadustat dosing
      regimens among chronic dialysis participants converted from ESA therapy or who are ESA-naïve.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Mean Hb Value ≥10 g/dL
time frame: Week 16 through Week 24
description: Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.
measure: Mean Hb Change From Baseline to Average Hb From Weeks 16-24
time frame: Baseline, Weeks 16-24
description: Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.
arm group label: Roxadustat
arm group type: Experimental
description: Participants will receive roxadustat as an oral tablet, 3 times per week (TIW) for up to a maximum of 24 weeks. If a participant requires roxadustat <60 milligrams (mg)/week to maintain Hb levels, the dose frequency will be reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from CERA, the initial roxadustat dose will be based on the average prescribed CERA dose in the last 8 weeks prior to conversion. For participants with <6 weeks of prior CERA use, the initial roxadustat dose will be based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations will be made every 4 weeks and doses will be titrated based on Hb level and rate of Hb change. The prescribed dose will not exceed the maximum allowable dose of 3.0 mg/kilogram (kg)/dose or 400 mg per dose, whichever is lower.
intervention type: Drug
intervention name: Roxadustat
description: Roxadustat will be administered per dose and schedule specified in the arm description.
arm group label: Roxadustat
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Eisner
role: Study Chair
affiliation: FibroGen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Failure, Chronic
mesh term: Anemia
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 