<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/NCT03019185</url>
  </required_header>
  <id_info>
    <org_study_id>RTA 402-C-1603</org_study_id>
    <nct_id>NCT03019185</nct_id>
  </id_info>
  <brief_title>A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL</brief_title>
  <acronym>CARDINAL</acronym>
  <official_title>A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Reata Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Reata Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and&#xD;
      efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2&#xD;
      portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of&#xD;
      the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and&#xD;
      efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2&#xD;
      portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of&#xD;
      the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180&#xD;
      patients.&#xD;
&#xD;
      Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients&#xD;
      in the Phase 3 cohort will be randomized 1:1 to either bardoxolone methyl or placebo and&#xD;
      randomization will be stratified by baseline albumin to creatinine ratio (ACR). Patients&#xD;
      randomized to placebo will remain on placebo throughout the study, undergoing sham titration.&#xD;
&#xD;
      All patients in the study will follow the same visit and assessment schedule. Following&#xD;
      randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks&#xD;
      1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 and by telephone contact on Days&#xD;
      3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal&#xD;
      period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they&#xD;
      received at Week 48 and will continue study drug treatment through Week 100. Patients will&#xD;
      also be scheduled to be assessed at an in person follow up visit at Week 104, four weeks&#xD;
      after the end of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2017</start_date>
  <completion_date type="Actual">October 30, 2020</completion_date>
  <primary_completion_date type="Actual">October 6, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Increase in eGFR from baseline</measure>
    <time_frame>48 weeks</time_frame>
    <description>To assess the increase in eGFR from baseline to week 12 (Phase 2) or week 48 (Phase 3) for patients receiving active drug, compared to patients receiving placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Increase in eGFR from baseline following a 4-week drug treatment withdrawal period</measure>
    <time_frame>52 weeks</time_frame>
    <description>To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 52 following a 4-week drug treatment withdrawal period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>100 weeks</time_frame>
    <description>Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 100 weeks.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">187</enrollment>
  <condition>Alport Syndrome</condition>
  <arm_group>
    <arm_group_label>Phase 2 Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients with baseline ACR ≤ 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR &gt; 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (≥ 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR &gt;300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 3 Bardoxolone Cohort</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with baseline ACR ≤ 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR &gt; 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (≥ 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR &gt;300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 3 Placebo Cohort</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Capsule containing an inert placebo</description>
    <arm_group_label>Phase 3 Placebo Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bardoxolone Methyl</intervention_name>
    <description>Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.</description>
    <arm_group_label>Phase 2 Cohort</arm_group_label>
    <arm_group_label>Phase 3 Bardoxolone Cohort</arm_group_label>
    <other_name>RTA 402</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients 12 ≤ age ≤ 60 upon study consent;&#xD;
&#xD;
          -  Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene&#xD;
             associated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologic&#xD;
             assessment using electron microscopy;&#xD;
&#xD;
          -  Screening eGFR ≥ 30 and ≤ 90 mL/min/1.73 m2. The two eGFR values collected at Screen A&#xD;
             and Screen B visits used to determine eligibility must have a percent difference ≤&#xD;
             25%;&#xD;
&#xD;
          -  Albumin to creatinine ratio (ACR) ≤ 3500 mg/g at Screen B visit;&#xD;
&#xD;
          -  If receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II&#xD;
             receptor blocker (ARB), the medications must remain the same for at least 6 weeks&#xD;
             prior to the Screen A visit and during Screening. The dosage of ACE inhibitor and/or&#xD;
             ARB must also be stable for 2 weeks prior to the Screen A visit and remain the same&#xD;
             through Day 1 (i.e., no change in dosage or medication). Patients not taking an ACE&#xD;
             inhibitor and/or ARB because of a medical contraindication must have discontinued&#xD;
             treatment at least 8 weeks prior to the Screen A visit;&#xD;
&#xD;
          -  Adequate bone marrow reserve and organ function at the Screen A visit&#xD;
&#xD;
          -  Able to swallow capsules;&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other study procedures;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to bardoxolone methyl;&#xD;
&#xD;
          -  Ongoing chronic hemodialysis or peritoneal dialysis therapy;&#xD;
&#xD;
          -  Renal transplant recipient;&#xD;
&#xD;
          -  B-type natriuretic peptide (BNP) level &gt; 200 pg/mL at Screen A visit;&#xD;
&#xD;
          -  Uncontrolled diabetes (HbA1c &gt; 11.0%) at Screen A visit;&#xD;
&#xD;
          -  Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or&#xD;
             during Screening;&#xD;
&#xD;
          -  Serum albumin &lt; 3 g/dL at Screen A visit;&#xD;
&#xD;
          -  History of clinically significant left-sided heart disease and/or clinically&#xD;
             significant cardiac disease, including but not limited to any of the following:&#xD;
&#xD;
          -  Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure&#xD;
             (BP) &gt; 160 mm Hg or sitting diastolic BP &gt; 100 mm Hg at Screen A visit after a period&#xD;
             of rest;&#xD;
&#xD;
          -  Systolic BP &lt; 90 mm Hg at Screen A visit after a period of rest;&#xD;
&#xD;
          -  History of malignancy within 5 years prior to Screen A visit, with the exception of&#xD;
             localized skin or cervical carcinomas;&#xD;
&#xD;
          -  Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks&#xD;
             prior to randomization or anticipated need for immunosuppression during the study;&#xD;
&#xD;
          -  Untreated or uncontrolled active bacterial, fungal, or viral infection;&#xD;
&#xD;
          -  Participation in other interventional clinical studies within 30 days prior to Day 1;&#xD;
&#xD;
          -  Unwilling to practice acceptable methods of birth control (both males who have&#xD;
             partners of child-bearing potential and females of childbearing potential) during&#xD;
             Screening, while taking study drug, and for at least 30 days after the last dose of&#xD;
             study drug is ingested;&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding;&#xD;
&#xD;
          -  Known hypersensitivity to any component of the study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Kidney Disease and Hypertension Research Services, PLLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scripps Clinic, Nephrology</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Research Institute</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>David Geffen School of Medicine at UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Clinical Research Center - Parnassus</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco - Children's Renal Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver Nephrologists PC</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Florida Research Institute</name>
      <address>
        <city>Lauderdale Lakes</city>
        <state>Florida</state>
        <zip>33313</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine and Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boise Kidney &amp; Hypertension Institute</name>
      <address>
        <city>Caldwell</city>
        <state>Idaho</state>
        <zip>83605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boise Kidney &amp; Hypertension Institute</name>
      <address>
        <city>Meridian</city>
        <state>Idaho</state>
        <zip>83642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University Health System</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Biolab Research, LLC</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20852</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota - Division of Pediatric Nephrology</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Research Institute - The Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack Meridian School of Medicine</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nephrology Associates, PC</name>
      <address>
        <city>Flushing</city>
        <state>New York</state>
        <zip>11355</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Nephrology</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brookview Hills Research Associates, PLLC</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akron Nephrology Associates</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akron Children's Hospital</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia (CHOP)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh School of Medicine - Division of Pediatric Nephrology</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Warren Alpert Medical School of Brown University</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Carolina Nephrology &amp; Hypertension Center, Inc</name>
      <address>
        <city>Orangeburg</city>
        <state>South Carolina</state>
        <zip>29118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renal Disease Research Institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Houston Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77099</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Advancement Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Health</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Clinical Research</name>
      <address>
        <city>West Jordan</city>
        <state>Utah</state>
        <zip>84088</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Melbourne Renal Research Group</name>
      <address>
        <city>Melbourne</city>
        <zip>VIC 3073</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>New Lambton Heights</city>
        <zip>NSW 2305</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sydney Children's Hospital</name>
      <address>
        <city>Sydney</city>
        <zip>NSW 2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Westmead</name>
      <address>
        <city>Westmead</city>
        <zip>NSW 2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble- Grenoble France</name>
      <address>
        <city>La Tronche</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Lyon-Hopital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Necker-Universite Paris Descartes</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Medicine Gottingen</name>
      <address>
        <city>Göttingen</city>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Children's Hospital Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Marianna University Hospital</name>
      <address>
        <city>Kawasaki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe University Hospital</name>
      <address>
        <city>Kobe</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Nagoya Daini Hospital</name>
      <address>
        <city>Nagoya</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JCHO Cyukyo Hospital</name>
      <address>
        <city>Nagoya</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kitano Hospital</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saga University Hospital</name>
      <address>
        <city>Saga</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Children's Medical Center</name>
      <address>
        <city>Saitama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JCHO Sendai Hospital</name>
      <address>
        <city>Sendai</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juntendo University Hospital</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Metropolitan Children's Medical Center</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Puerto Rico Clinical &amp; Translational Research Center</name>
      <address>
        <city>Rio Piedras</city>
        <zip>00935</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Servicio de Nefrologia pediatrica</name>
      <address>
        <city>Barcelona</city>
        <zip>119-08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacio Puigvert</name>
      <address>
        <city>Barcelona</city>
        <zip>340-08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Arrixaca</name>
      <address>
        <city>El Palmar</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Puerto Rico</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <disposition_first_submitted>September 22, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>September 22, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 28, 2021</disposition_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alport Syndrome</keyword>
  <keyword>Bardoxolone methyl</keyword>
  <keyword>CDDO-ME</keyword>
  <keyword>RTA 402</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephritis, Hereditary</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03019185
org study id: RTA 402-C-1603
nct id: NCT03019185
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and
      efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2
      portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of
      the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180
      patients.
This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and
      efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2
      portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of
      the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180
      patients.

      Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients
      in the Phase 3 cohort will be randomized 1:1 to either bardoxolone methyl or placebo and
      randomization will be stratified by baseline albumin to creatinine ratio (ACR). Patients
      randomized to placebo will remain on placebo throughout the study, undergoing sham titration.

      All patients in the study will follow the same visit and assessment schedule. Following
      randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks
      1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 and by telephone contact on Days
      3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal
      period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they
      received at Week 48 and will continue study drug treatment through Week 100. Patients will
      also be scheduled to be assessed at an in person follow up visit at Week 104, four weeks
      after the end of treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Increase in eGFR from baseline
time frame: 48 weeks
description: To assess the increase in eGFR from baseline to week 12 (Phase 2) or week 48 (Phase 3) for patients receiving active drug, compared to patients receiving placebo.
measure: Increase in eGFR from baseline following a 4-week drug treatment withdrawal period
time frame: 52 weeks
description: To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 52 following a 4-week drug treatment withdrawal period.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 100 weeks
description: Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 100 weeks.
arm group label: Phase 2 Cohort
arm group type: Experimental
description: Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients with baseline ACR ≤ 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR > 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (≥ 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.
arm group label: Phase 3 Bardoxolone Cohort
arm group type: Active Comparator
description: Patients with baseline ACR ≤ 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR > 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (≥ 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.
arm group label: Phase 3 Placebo Cohort
arm group type: Placebo Comparator
description: Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Capsule containing an inert placebo
arm group label: Phase 3 Placebo Cohort
intervention type: Drug
intervention name: Bardoxolone Methyl
description: Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.
arm group label: Phase 2 Cohort
arm group label: Phase 3 Bardoxolone Cohort
other name: RTA 402
criteria: 
gender: All
minimum age: 12 Years
maximum age: 60 Years
healthy volunteers: No
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country: Australia
country: France
country: Germany
country: Japan
country: Puerto Rico
country: Spain
country: United Kingdom
country: United States
country: Canada
responsible party type: Sponsor
mesh term: Nephritis, Hereditary
mesh term: Syndrome