<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/NCT04488822</url>
  </required_header>
  <id_info>
    <org_study_id>PL3397-A-A303</org_study_id>
    <nct_id>NCT04488822</nct_id>
  </id_info>
  <brief_title>A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT</brief_title>
  <acronym>PLX3397</acronym>
  <official_title>Multicenter, Single Arm Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, Inc.</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess pexidartinib in adult participants with symptomatic TGCT that is&#xD;
      associated with severe morbidity or functional limitations and not amendable to improvement&#xD;
      with surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants with symptomatic TGCT will be administered pexidartinib 400 mg twice daily&#xD;
      continuously with 28-day treatment cycle until criteria for discontinuation are reached.&#xD;
      Participants who complete primary endpoint assessments may be eligible to continue receiving&#xD;
      pexidartinib until disease progression, unacceptable toxicity, the occurrence of other&#xD;
      termination criteria, or withdrawal from the study. Eligible participants' status will be&#xD;
      collected every 6 months as a long term follow-up at least 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 25, 2020</start_date>
  <completion_date type="Anticipated">March 30, 2024</completion_date>
  <primary_completion_date type="Actual">October 27, 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>Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</measure>
    <time_frame>At Week 25 postdose</time_frame>
    <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</measure>
    <time_frame>At Week 25 postdose</time_frame>
    <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib</measure>
    <time_frame>At Week 25 postdose</time_frame>
    <description>Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib</measure>
    <time_frame>At Week 25 postdose</time_frame>
    <description>The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan</measure>
    <time_frame>From baseline until disease progression or death (whichever occurs first), up to approximately 29 months</time_frame>
    <description>Best overall response (CR or PR) of pexidartinib based on RECIST 1.1 and TVS are summarized. Tumor categories for RECIST v1.1 were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions; and not evaluable (NE). Tumor categories for TVS were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 50% decrease in volume score relative to baseline; stable disease (SD), does not meet any of the prior criteria based on score during study; progressive disease (PD), at least a 30% increase in in volume relative to lowest score during the study whether at baseline or some other visit; and not evaluable (NE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan</measure>
    <time_frame>Time from the date of first documented response until documented disease progression or death from any cause (whichever occurs first), up to approximately 29 months</time_frame>
    <description>Duration of response (DOR) is defined as the date of the first recorded response to the first date of documented disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term</measure>
    <time_frame>Up to approximately 29 months</time_frame>
    <description>A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib</measure>
    <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
    <description>AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib</measure>
    <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
    <description>Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib</measure>
    <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
    <description>Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Tenosynovial Giant Cell Tumor</condition>
  <arm_group>
    <arm_group_label>Pexidartinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pexidartinib</intervention_name>
    <description>400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)</description>
    <arm_group_label>Pexidartinib</arm_group_label>
    <other_name>TURALIO™</other_name>
    <other_name>PLX3397</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years (Age ≥ 20 years in Taiwan).&#xD;
&#xD;
          -  A diagnosis of TGCT (i) that has been histologically confirmed by a pathologist and&#xD;
             (ii) associated with severe morbidity or functional limitations and not amenable to&#xD;
             improvement with surgery determined consensually by qualified personnel (eg, 2&#xD;
             surgeons or a multi-disciplinary tumor board).&#xD;
&#xD;
          -  Measurable disease as defined by RECIST 1.1 (except that a minimal size of 2 cm is&#xD;
             required), assessed from MRI scan by a central radiologist.&#xD;
&#xD;
          -  Stable prescription of analgesic regimen during the 2 weeks prior to enrollment.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test within the&#xD;
             14-day period prior to enrollment (Where demanded by local regulations, this test may&#xD;
             be required within 72 hours of enrollment).&#xD;
&#xD;
          -  Females of reproductive potential should be advised to use an effective, non-hormonal&#xD;
             method of contraception during treatment with pexidartinib and for 1 month after the&#xD;
             last dose. Males with female partners of reproductive potential should be advised to&#xD;
             use an effective method of contraception during treatment with pexidartinib and for 1&#xD;
             month after the last dose. Female partners of male participants should concurrently&#xD;
             use effective contraceptive methods (hormonal or non-hormonal). Women of&#xD;
             nonchildbearing potential may be included if they are either surgically sterile or&#xD;
             have been postmenopausal for ≥ 1 year. Women who have documentation of at least 12&#xD;
             months of spontaneous amenorrhea and have a follicle stimulating hormone level &gt; 40&#xD;
             mIU/mL will be considered postmenopausal.&#xD;
&#xD;
          -  Adequate hematologic, hepatic, and renal function, defined by:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1.5 × 109/L&#xD;
&#xD;
               -  Hemoglobin &gt; 10 g/dL&#xD;
&#xD;
               -  Platelet count ≥ 100 × 109/L&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.0 × upper&#xD;
                  limit of normal (ULN)&#xD;
&#xD;
               -  Total bilirubin and direct bilirubin ≤ 1.0 × ULN&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 1.0 × ULN&#xD;
&#xD;
               -  Creatinine clearance (CLcr) &gt; 15 mL/min&#xD;
&#xD;
          -  Willingness and ability to complete the PROMIS Physical Function Scale.&#xD;
&#xD;
          -  Willingness and ability to use a diary.&#xD;
&#xD;
          -  Willingness and ability to provide written informed consent prior to any study-related&#xD;
             procedures and to comply with all study requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Investigational drug/device use within 28 days of enrolment.&#xD;
&#xD;
          -  Previous use of pexidartinib or any biologic treatment targeting colony stimulating&#xD;
             factor 1 (CSF-1) or the CSF-1 receptor; previous use of oral tyrosine kinase&#xD;
             inhibitors are allowed (eg, imatinib or nilotinib).&#xD;
&#xD;
          -  Active cancer except for tumor for which a participant is enrolled in the study,&#xD;
             (either concurrent or within the last year of starting study drug) that requires&#xD;
             therapy (eg, surgical, chemotherapy, or radiation therapy), with the exception of&#xD;
             adequately treated basal or squamous cell carcinoma of the skin, melanoma in situ,&#xD;
             carcinoma in situ of the cervix or breast, or prostate carcinoma with a&#xD;
             prostate-specific antigen value &lt; 0.2 ng/mL.&#xD;
&#xD;
          -  Known metastatic TGCT.&#xD;
&#xD;
          -  Active or chronic infection with hepatitis C or known positive hepatitis B surface&#xD;
             antigen, or known active or chronic infection with human immunodeficiency virus.&#xD;
&#xD;
          -  Active liver or biliary tract disease&#xD;
&#xD;
          -  Known active tuberculosis.&#xD;
&#xD;
          -  Significant concomitant arthropathy in the affected joint, serious illness,&#xD;
             uncontrolled infection, or a medical or psychiatric history that, in the&#xD;
             Investigator's opinion, would likely interfere with a participant's study&#xD;
             participation or the interpretation of his or her results.&#xD;
&#xD;
          -  Use of strong Cytochrome P450 (CYP) 3A inducers, including St John's wort, proton pump&#xD;
             inhibitors (PPIs), and other products known to cause hepatotoxicity.&#xD;
&#xD;
          -  Women who are breastfeeding.&#xD;
&#xD;
          -  A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms&#xD;
             (women).&#xD;
&#xD;
          -  MRI contraindications.&#xD;
&#xD;
          -  History of hypersensitivity to any excipients in the investigational product.&#xD;
&#xD;
          -  Inability to swallow capsules.&#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>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Ji Shui Tan Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <results_first_submitted>February 21, 2023</results_first_submitted>
  <results_first_submitted_qc>April 4, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 27, 2023</results_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tenosynovial Giant Cell Tumor</keyword>
  <keyword>Pexidartinib</keyword>
  <keyword>TURALIO™</keyword>
  <keyword>PLX3397</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Giant Cell Tumors</mesh_term>
    <mesh_term>Giant Cell Tumor of Tendon Sheath</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT04488822/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 40 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at clinic centers in China and Taiwan. Primary results reported are from baseline up to data cut-off date of 27 Oct 2021. The results presented are based on primary analysis. Data collection is still on-going and additional results will be provided after study completion.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Pexidartinib</title>
          <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</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>Baseline characteristics were assessed in the Safety Analysis Set.</population>
      <group_list>
        <group group_id="B1">
          <title>Pexidartinib</title>
          <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.9" spread="12.05"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Taiwan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</title>
        <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.</description>
        <time_frame>At Week 25 postdose</time_frame>
        <population>ORR based on RECIST 1.1 was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</title>
          <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.</description>
          <population>ORR based on RECIST 1.1 was assessed in the Full Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ORR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</title>
        <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.</description>
        <time_frame>At Week 25 postdose</time_frame>
        <population>ORR based on TVS was assessed in the Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25</title>
          <description>For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.</description>
          <population>ORR based on TVS was assessed in the Full Analysis Set.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ORR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib</title>
        <description>Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.</description>
        <time_frame>At Week 25 postdose</time_frame>
        <population>Mean Percent Change From Baseline for Range of Motion (ROM) was assessed in Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib</title>
          <description>Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.</description>
          <population>Mean Percent Change From Baseline for Range of Motion (ROM) was assessed in Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.</population>
          <units>Percent Change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.05" spread="3.207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib</title>
        <description>The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.</description>
        <time_frame>At Week 25 postdose</time_frame>
        <population>Mean Change From PROMIS was assessed in the Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib</title>
          <description>The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.</description>
          <population>Mean Change From PROMIS was assessed in the Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.</population>
          <units>Score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="1.384"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan</title>
        <description>Best overall response (CR or PR) of pexidartinib based on RECIST 1.1 and TVS are summarized. Tumor categories for RECIST v1.1 were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions; and not evaluable (NE). Tumor categories for TVS were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 50% decrease in volume score relative to baseline; stable disease (SD), does not meet any of the prior criteria based on score during study; progressive disease (PD), at least a 30% increase in in volume relative to lowest score during the study whether at baseline or some other visit; and not evaluable (NE).</description>
        <time_frame>From baseline until disease progression or death (whichever occurs first), up to approximately 29 months</time_frame>
        <posting_date>03/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan</title>
        <description>Duration of response (DOR) is defined as the date of the first recorded response to the first date of documented disease progression.</description>
        <time_frame>Time from the date of first documented response until documented disease progression or death from any cause (whichever occurs first), up to approximately 29 months</time_frame>
        <posting_date>03/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term</title>
        <description>A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).</description>
        <time_frame>Up to approximately 29 months</time_frame>
        <posting_date>03/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib</title>
        <description>AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
        <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
        <population>AUC(0-6h) was assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib</title>
          <description>AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
          <population>AUC(0-6h) was assessed in the Pharmacokinetic Analysis Set.</population>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pexidartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51500" spread="28.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ZAAD-1006a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108000" spread="52.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib</title>
        <description>Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
        <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
        <population>Cmax was assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib</title>
          <description>Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
          <population>Cmax was assessed in the Pharmacokinetic Analysis Set.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pexidartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12400" spread="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ZAAD-1006a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20400" spread="46.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib</title>
        <description>Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
        <time_frame>Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)</time_frame>
        <population>Tmax was assessed in the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Pexidartinib</title>
            <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib</title>
          <description>Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.</description>
          <population>Tmax was assessed in the Pharmacokinetic Analysis Set.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pexidartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.08" lower_limit="0.87" upper_limit="2.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ZAAD-1006a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12" lower_limit="1.80" upper_limit="5.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AE) were collected from the date of signing the informed consent form up post-treatment visit (28 ± 7 days after the last dose of study drug), up 13 months.</time_frame>
      <desc>A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).</desc>
      <group_list>
        <group group_id="E1">
          <title>Pexidartinib</title>
          <description>Participants who received pexidartinib 400mg twice daily (BID) for a total daily dose of 800 mg (2 capsules in the morning and 2 capsules in the evening).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.1</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="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fistula inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Epithelioid sarcoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 24.1</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="40" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Periorbital oedema</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Eyelid oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Swelling face</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Bilirubin conjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood cholinesterase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Monocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>High density lipoprotein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Low density lipoprotein decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total bile acids increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Enzyme abnormality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Taste disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </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="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hair color changes</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Skin discoloration</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hair texture abnormal</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Director</name_or_title>
      <organization>Daiichi Sankyo, Inc.</organization>
      <phone>908-992-6400</phone>
      <email>CTRinfo@dsi.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/NCT04488822
org study id: PL3397-A-A303
nct id: NCT04488822
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will assess pexidartinib in adult participants with symptomatic TGCT that is
      associated with severe morbidity or functional limitations and not amendable to improvement
      with surgery.
Participants with symptomatic TGCT will be administered pexidartinib 400 mg twice daily
      continuously with 28-day treatment cycle until criteria for discontinuation are reached.
      Participants who complete primary endpoint assessments may be eligible to continue receiving
      pexidartinib until disease progression, unacceptable toxicity, the occurrence of other
      termination criteria, or withdrawal from the study. Eligible participants' status will be
      collected every 6 months as a long term follow-up at least 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) of Pexidartinib Based on RECIST 1.1 of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25
time frame: At Week 25 postdose
description: For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.
measure: Overall Response Rate (ORR) of Pexidartinib Based on TVS of Asian Participants With Symptomatic Tenosynovial Giant Cell Tumor (TGCT) at Week 25
time frame: At Week 25 postdose
description: For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.
measure: Mean Percent Change From Baseline for Range of Motion (ROM) Score in Participants Receiving Pexidartinib
time frame: At Week 25 postdose
description: Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.
measure: Mean Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score in Participants Receiving Pexidartinib
time frame: At Week 25 postdose
description: The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.
measure: Best Overall Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan
time frame: From baseline until disease progression or death (whichever occurs first), up to approximately 29 months
description: Best overall response (CR or PR) of pexidartinib based on RECIST 1.1 and TVS are summarized. Tumor categories for RECIST v1.1 were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions; and not evaluable (NE). Tumor categories for TVS were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 50% decrease in volume score relative to baseline; stable disease (SD), does not meet any of the prior criteria based on score during study; progressive disease (PD), at least a 30% increase in in volume relative to lowest score during the study whether at baseline or some other visit; and not evaluable (NE).
measure: Duration of Response of Pexidartinib Based on RECIST 1.1 and TVS by Centrally Reviewed MRI Scan
time frame: Time from the date of first documented response until documented disease progression or death from any cause (whichever occurs first), up to approximately 29 months
description: Duration of response (DOR) is defined as the date of the first recorded response to the first date of documented disease progression.
measure: Number of Participants Reporting Frequent (≥10%) Treatment-Emergent Adverse Events by Preferred Term
time frame: Up to approximately 29 months
description: A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).
measure: Area Under the Plasma Concentration Time Curve From Time 0 to 6 Hours AUC(0-6h) in Participants Receiving Pexidartinib
time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
description: AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.
measure: Maximum Plasma Concentration (Cmax) in Participants Receiving Pexidartinib
time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
description: Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Participants Receiving Pexidartinib
time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)
description: Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.
arm group label: Pexidartinib
arm group type: Experimental
intervention type: Drug
intervention name: Pexidartinib
description: 400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)
arm group label: Pexidartinib
other name: TURALIO™
other name: PLX3397
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
country: Taiwan
responsible party type: Sponsor
mesh term: Giant Cell Tumors
mesh term: Giant Cell Tumor of Tendon Sheath
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 