<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/NCT03755518</url>
  </required_header>
  <id_info>
    <org_study_id>FEDR-MF-001</org_study_id>
    <secondary_id>U1111-1223-2862</secondary_id>
    <secondary_id>2018-002237-38</secondary_id>
    <nct_id>NCT03755518</nct_id>
  </id_info>
  <brief_title>A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib</brief_title>
  <acronym>FREEDOM</acronym>
  <official_title>A Phase 3b, Multicenter, Single-Arm, Open-Label Efficacy and Safety Study of Fedratinib in Subjects With DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High-Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF) and Previously Treated With Ruxolitinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS&#xD;
      (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary&#xD;
      Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential&#xD;
      Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.&#xD;
&#xD;
      The primary objective of the study is to evaluate the percentage of subjects with at least a&#xD;
      35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of&#xD;
      fedratinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS&#xD;
      (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary&#xD;
      Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential&#xD;
      Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.&#xD;
&#xD;
      The spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary&#xD;
      objectives of the study are to further evaluate the safety and to assess and implement&#xD;
      mitigation strategies for WE and for gastrointestinal (GI) adverse events.&#xD;
&#xD;
      The study will be at multiple centers to provide access to a broad population and have&#xD;
      assurance the results are likely to have general applicability.&#xD;
&#xD;
      This is also conducted as an open-label study to collect efficacy and safety data with&#xD;
      fedratinib use, no randomization or stratification will occur.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 27, 2019</start_date>
  <completion_date type="Anticipated">September 29, 2023</completion_date>
  <primary_completion_date type="Actual">November 26, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs</measure>
    <time_frame>From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 128 weeks)</time_frame>
    <description>Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs</measure>
    <time_frame>From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
    <description>Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in hematology laboratory analysis - hemoglobin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in hematology laboratory analysis - erythrocytes.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in hematology laboratory analysis - blasts/leukocytes&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine</measure>
    <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
    <description>Mean change from baseline in chemistry parameters analysis - Creatinine.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spleen Response Rate by Palpation</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptom Response Rate</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS &gt; 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of Spleen Volume Response by MRI/CT (DR)</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction &lt; 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of Spleen Response by Palpation (DRP)</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of Symptom Response (DSR)</measure>
    <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
    <description>Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction &lt; 50%. In the absence of TSS reduction &lt; 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.</measure>
    <time_frame>From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
    <description>Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Thiamine Levels &lt; Lower Limit of Normal (LLN).</measure>
    <time_frame>At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
    <description>Number of participants with thiamine levels &lt; LLN.&#xD;
LLN of thiamine is 70 nmol/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Thiamine Levels &gt; Upper Limit of Normal (ULN).</measure>
    <time_frame>At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
    <description>Number of participants with thiamine levels &gt; ULN.&#xD;
ULN of thiamine is 180 nmol/L.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Primary Myelofibrosis</condition>
  <condition>Post-Polycythemia Vera Myelofibrosis</condition>
  <condition>Myelofibrosis</condition>
  <condition>Post-essential Thrombocythemia Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>Administration of Fedratinib 400mg/day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Self-administered Investigational Product (IP) (400 mg/day) on an outpatient basis, once daily preferably with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FEDRATINIB</intervention_name>
    <description>A potent and selective inhibitor of JAK2 kinase activity</description>
    <arm_group_label>Administration of Fedratinib 400mg/day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Main Study Inclusion Criteria&#xD;
&#xD;
          1. Subject is at least 18 years of age at the time of signing the informed consent form&#xD;
             (ICF)&#xD;
&#xD;
          2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0,&#xD;
             1 or 2&#xD;
&#xD;
          3. Subject has diagnosis of primary myelofibrosis (PMF) according to the 2016 World&#xD;
             Health Organization (WHO) criteria, or diagnosis of post-ET or post-PV myelofibrosis&#xD;
             according to the IWG-MRT 2007 criteria, confirmed by the most recent local pathology&#xD;
             report&#xD;
&#xD;
          4. Subject has a DIPSS Risk score of Intermediate or High&#xD;
&#xD;
          5. Subject has a measurable splenomegaly during the screening period as demonstrated by&#xD;
             spleen volume of ≥ 450 cm3 by MRI or CT-scan assessment or by palpable spleen&#xD;
             measuring ≥ 5 cm below the left costal margin.&#xD;
&#xD;
          6. Subject has been previously exposed to ruxolitinib, while diagnosed with MF (PMF,&#xD;
             post-ET MF or post-PV MF), and must meet at least one of the following criteria (a or&#xD;
             b)&#xD;
&#xD;
               1. Treatment with ruxolitinib for ≥ 3 months&#xD;
&#xD;
               2. Treatment with ruxolitinib for ≥ 28 days complicated by any of the following:&#xD;
&#xD;
                    -  Development of a red blood cell transfusion requirement (at least 2&#xD;
                       units/month for 2 months) or&#xD;
&#xD;
                    -  Grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while&#xD;
                       on treatment with ruxolitinib&#xD;
&#xD;
          7. Subject must have treatment-related toxicities from prior therapy resolved to Grade 1&#xD;
             or pretreatment baseline before start of last therapy prior to fedratinib treatment.&#xD;
&#xD;
          8. Subject must understand and voluntarily sign an ICF prior to any study-related&#xD;
             assessments/procedures being conducted&#xD;
&#xD;
          9. Subject is willing and able to adhere to the study visit schedule and other protocol&#xD;
             requirements&#xD;
&#xD;
         10. Participants must agree to use effective contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Main Study Exclusion Criteria&#xD;
&#xD;
          1. Any of the following laboratory abnormalities:&#xD;
&#xD;
               1. Platelets &lt; 50,000/μL&#xD;
&#xD;
               2. Absolute neutrophil count (ANC) &lt; 1.0 x 109/L&#xD;
&#xD;
               3. White blood count (WBC) &gt; 100 x 10^9/L&#xD;
&#xD;
               4. Myeloblasts &gt; 5 % in peripheral blood&#xD;
&#xD;
               5. Estimated glomerular filtration rate &lt; 30 mL/min/1.73 m^2 (as per the&#xD;
                  Modification of Diet in Renal Disease [MDRD] formula)&#xD;
&#xD;
               6. Serum amylase or lipase &gt; 1.5 x ULN (upper limit of normal)&#xD;
&#xD;
               7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 3 x ULN&#xD;
&#xD;
               8. Total bilirubin &gt; 1.5 x ULN, subject's total bilirubin between 1.5 - 3.0 x ULN&#xD;
                  are eligible if the direct bilirubin fraction is &lt; 25% of the total bilirubin&#xD;
&#xD;
          2. Subject is pregnant or lactating female&#xD;
&#xD;
          3. Subject with previous splenectomy&#xD;
&#xD;
          4. Subject with previous or planned hematopoietic cell transplant&#xD;
&#xD;
          5. Subject with prior history of encephalopathy, including Wernicke's&#xD;
&#xD;
          6. Subject with signs or symptoms of encephalopathy including Wernicke's (eg, severe&#xD;
             ataxia, ocular paralysis or cerebellar signs)&#xD;
&#xD;
          7. Subject with thiamine deficiency, defined as thiamine levels in whole blood below&#xD;
             normal range according to institutional standard and not corrected prior to enrollment&#xD;
             on the study&#xD;
&#xD;
          8. Subject with concomitant treatment with or use of pharmaceutical, herbal agents or&#xD;
             food known to be strong or moderate inducers of Cytochrome P450 3A4 (CYP3A4), or dual&#xD;
             CYP2C19 and CYP3A4 inhibitors&#xD;
&#xD;
          9. Subject on any chemotherapy, immunomodulatory drug therapy (eg, thalidomide,&#xD;
             interferon-alpha), anagrelide, immunosuppressive therapy, systemic corticosteroids &gt;&#xD;
             10 mg/day prednisone or equivalent. Subjects who have had prior exposure to&#xD;
             hydroxyurea (eg, Hydrea) in the past may be enrolled into the study as long as it has&#xD;
             not been administered within 14 days prior to the start of fedratinib treatment&#xD;
&#xD;
         10. Subject has received ruxolitinib within 14 days prior to the start of fedratinib&#xD;
&#xD;
         11. Subject on treatment with myeloid growth factor (eg, granulocyte-colony stimulating&#xD;
             factor [G-CSF]) within 14 days prior to the start of fedratinib treatment&#xD;
&#xD;
         12. Subject with previous exposure to Janus kinase (JAK) inhibitor(s) for more than 1&#xD;
             cycle other than ruxolitinib treatment&#xD;
&#xD;
         13. Subject on treatment with aspirin with doses &gt; 150 mg daily&#xD;
&#xD;
         14. Subject with major surgery within 28 days before starting fedratinib treatment&#xD;
&#xD;
         15. Subject with diagnosis of chronic liver disease (eg, chronic alcoholic liver disease,&#xD;
             autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,&#xD;
             hemochromatosis, non-alcoholic steatohepatitis)&#xD;
&#xD;
         16. Subject with prior malignancy other than the disease under study unless the subject&#xD;
             has not required treatment for the malignancy for at least 3 years prior to&#xD;
             enrollment.&#xD;
&#xD;
             However, subject with the following history/concurrent conditions provided&#xD;
             successfully treated may enroll: non-invasive skin cancer, in situ cervical cancer,&#xD;
             carcinoma in situ of the breast, incidental histologic finding of prostate cancer (T1a&#xD;
             or T1b using the tumor, nodes, metastasis [TNM] clinical staging system), or is free&#xD;
             of disease and on hormonal treatment only&#xD;
&#xD;
         17. Subject with uncontrolled congestive heart failure (New York Heart Association&#xD;
             Classification 3 or 4)&#xD;
&#xD;
         18. Subject with known human immunodeficiency virus (HIV), known active infectious&#xD;
             Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC)&#xD;
&#xD;
         19. Subject with serious active infection&#xD;
&#xD;
         20. Subject with presence of any significant gastric or other disorder that would inhibit&#xD;
             absorption of oral medication&#xD;
&#xD;
         21. Subject is unable to swallow capsule&#xD;
&#xD;
         22. Subject has any significant medical condition, laboratory abnormality, or psychiatric&#xD;
             illness that would prevent the subject from participating in the study&#xD;
&#xD;
         23. Subject has any condition including the presence of laboratory abnormalities, which&#xD;
             places the subject at unacceptable risk if he/she were to participate in the study&#xD;
&#xD;
         24. Subject has any condition that confounds the ability to interpret data from the study&#xD;
&#xD;
         25. Subject with participation in any study of an investigational agent (drug, biologic,&#xD;
             device) within 30 days prior to start of fedratinib treatment&#xD;
&#xD;
         26. Subject with life expectancy of less than 6 months.&#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>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Local Institution - 117</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 126</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 113</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 112</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 109</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 121</name>
      <address>
        <city>Park Ridge</city>
        <state>Illinois</state>
        <zip>60068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 100</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160-7314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 123</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21229-5299</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 118</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 127</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <zip>21044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 103</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 101</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 128</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112-2027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 130</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 115</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 124</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 105</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 114</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 111</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 106</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 108</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 119</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-8852</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 132</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 110</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 120</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 116</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 129</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792-2454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 203</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 2A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 207</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6C 6B5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 205</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 200</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 201</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H1T 2M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 202</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 204</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1K 2R1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <link>
    <url>https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm</url>
    <description>FDA Safety Alerts and Recalls</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 8, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <results_first_submitted>November 22, 2022</results_first_submitted>
  <results_first_submitted_qc>February 13, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2023</results_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Myelofibrosis (MF)</keyword>
  <keyword>Primary Myelofibrosis (PMF)</keyword>
  <keyword>Post-Polycythemia Vera Myelofibrosis (Post-PV)</keyword>
  <keyword>Post-essential thrombocythemia Myelofibrosis (Post-ET)</keyword>
  <keyword>Myeloproliferative neoplasms (MPN)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycythemia Vera</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
    <mesh_term>Polycythemia</mesh_term>
    <mesh_term>Thrombocytosis</mesh_term>
    <mesh_term>Thrombocythemia, Essential</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 21, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03755518/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Fedratimib</title>
          <description>400 mg/day PO (4 x 100 mg capsules)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Bone Marrow Transplant</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by participant</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by investigator for non compliance</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Fedratimib</title>
          <description>400 mg/day PO (4 x 100 mg capsules)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="68.4" spread="7.69"/>
                  </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="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="5"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EE Population</title>
          <description>Efficacy Evaluable Population&#xD;
All participants who enrolled and received at least one dose of fedratinib, had an evaluable spleen volume at baseline (based on MRI/CT scan) and at least one post-baseline response assessment by MRI/CT scan</description>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MFSAF Population</title>
          <description>fedratinib treated participants with a Total Symptom Score (TSS) at baseline (eg, symptom score) &gt; 0 and at least 1 post baseline TSS assessment</description>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Palpation evaluable population</title>
          <description>All participants who enrolled and received at least one dose of fedratinib, and had an enlarged spleen ≥ 5 cm below LCM at baseline</description>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6</title>
        <description>Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>Efficacy evaluable population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6</title>
          <description>Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>Efficacy evaluable population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.7" lower_limit="12.5" upper_limit="43.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs</title>
        <description>Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.</description>
        <time_frame>From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 128 weeks)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs</title>
          <description>Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.</description>
          <population>Safety Population</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All grade</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs</title>
        <description>Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.</description>
        <time_frame>From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs</title>
          <description>Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.</description>
          <population>Safety Population</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All grade</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin</title>
        <description>Mean change from baseline in hematology laboratory analysis - hemoglobin</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin</title>
          <description>Mean change from baseline in hematology laboratory analysis - hemoglobin</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.16" spread="1.431"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.13" spread="1.127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes</title>
        <description>Mean change from baseline in hematology laboratory analysis - erythrocytes.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes</title>
          <description>Mean change from baseline in hematology laboratory analysis - erythrocytes.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>10¹²Cells/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.60" spread="0.567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.67" spread="0.609"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils</title>
        <description>Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils</title>
          <description>Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>10⁹Cells/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1 - platelets</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.8" spread="135.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - platelets</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.7" spread="131.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 4 day 1 - leukocytes</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.481" spread="21.6350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - leukocytes</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.127" spread="18.5744"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 4 day 1 - neutrophils</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.064" spread="14.2661"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - neutophils</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.495" spread="13.5489"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis</title>
        <description>Mean change from baseline in hematology laboratory analysis - blasts/leukocytes&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis</title>
          <description>Mean change from baseline in hematology laboratory analysis - blasts/leukocytes&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>Percentage of blasts/leukocytes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="1.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase</title>
        <description>Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase</title>
          <description>Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1 - ALT</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="18.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - ALT</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3" spread="29.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 4 day 1 - AST</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="8.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - AST</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="11.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 4 day 1 - Amylase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.1" spread="17.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - Amylase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" spread="15.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 4 day 1 - Lipase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="19.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - Lipase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="13.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine</title>
        <description>Mean change from baseline in chemistry parameters analysis - Creatinine.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
        <time_frame>at Cycle 4 Day 1 and Cycle 7 Day 1</time_frame>
        <population>all treated participants with both baseline and post-baseline measurements</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine</title>
          <description>Mean change from baseline in chemistry parameters analysis - Creatinine.&#xD;
Baseline value is defined as the last value or measurement taken prior to the first dose in the study</description>
          <population>all treated participants with both baseline and post-baseline measurements</population>
          <units>umol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cycle 4 day 1 - Creatinine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9" spread="18.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cycle 7 day 1 - Creatinine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.5" spread="23.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spleen Response Rate by Palpation</title>
        <description>Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>Palpation evaluable population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Spleen Response Rate by Palpation</title>
          <description>Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.</description>
          <population>Palpation evaluable population</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.2" lower_limit="6.2" upper_limit="32.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Symptom Response Rate</title>
        <description>Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS &gt; 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>MFSAF Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Symptom Response Rate</title>
          <description>Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS &gt; 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.</description>
          <population>MFSAF Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.4" lower_limit="27.9" upper_limit="61.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durability of Spleen Volume Response by MRI/CT (DR)</title>
        <description>Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction &lt; 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>EE population, Responders only</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Durability of Spleen Volume Response by MRI/CT (DR)</title>
          <description>Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction &lt; 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.</description>
          <population>EE population, Responders only</population>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="38.1" upper_limit="NA">Median and ULN not reached. 19 participants were censored. Insufficient number of events (subsequent progressive disease or deaths) occurred to calculate the median duration via the K-M method.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durability of Spleen Response by Palpation (DRP)</title>
        <description>Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>Palpation Evaluable Population, responders only</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Durability of Spleen Response by Palpation (DRP)</title>
          <description>Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.</description>
          <population>Palpation Evaluable Population, responders only</population>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="33.3" upper_limit="NA">Median and ULN not reached. 16 participants were censored. Insufficient number of events (subsequent progressive disease or deaths) occurred to calculate the median duration via the K-M method.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durability of Symptom Response (DSR)</title>
        <description>Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction &lt; 50%. In the absence of TSS reduction &lt; 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.</description>
        <time_frame>From First Dose to end of Cycle 6 (approximately 168 days)</time_frame>
        <population>MFSAF population, Responders only</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Durability of Symptom Response (DSR)</title>
          <description>Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction &lt; 50%. In the absence of TSS reduction &lt; 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.</description>
          <population>MFSAF population, Responders only</population>
          <units>Weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.1" lower_limit="11.0" upper_limit="31.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.</title>
        <description>Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.</description>
        <time_frame>From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.</title>
          <description>Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.</description>
          <population>Safety Population</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vomitting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Encephalopathy including Wernicke's</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Thiamine Levels &lt; Lower Limit of Normal (LLN).</title>
        <description>Number of participants with thiamine levels &lt; LLN.&#xD;
LLN of thiamine is 70 nmol/L.</description>
        <time_frame>At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Thiamine Levels &lt; Lower Limit of Normal (LLN).</title>
          <description>Number of participants with thiamine levels &lt; LLN.&#xD;
LLN of thiamine is 70 nmol/L.</description>
          <population>Safety Population</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 27</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Thiamine Levels &gt; Upper Limit of Normal (ULN).</title>
        <description>Number of participants with thiamine levels &gt; ULN.&#xD;
ULN of thiamine is 180 nmol/L.</description>
        <time_frame>At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Fedratimib</title>
            <description>400 mg/day PO (4 x 100 mg capsules)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Thiamine Levels &gt; Upper Limit of Normal (ULN).</title>
          <description>Number of participants with thiamine levels &gt; ULN.&#xD;
ULN of thiamine is 180 nmol/L.</description>
          <population>Safety Population</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="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 27</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 30</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events: From first dose up to 30 days post last dose. (An average of 50.3 weeks up to a maximum of 124 weeks) All Cause Mortality: From first dose up to LPLV PE final Database lock: approximately 2 years and 11 months.</time_frame>
      <desc>Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.</desc>
      <group_list>
        <group group_id="E1">
          <title>Fedratinib</title>
          <description>400 mg/day PO (4 x 100 mg capsules)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>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="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="38"/>
              </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="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Splenomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Cardiac tamponade</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Anal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Laryngeal squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neuroendocrine carcinoma of the skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>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="38" subjects_at_risk="38"/>
              </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="22" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal hernia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Early satiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Blast cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Glomerular filtration rate decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vitamin B1 decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </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="7" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </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="6" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Disturbance in attention</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </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="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Bristol-Myers Squibb Study Director</name_or_title>
      <organization>Bristol-Myers Squibb</organization>
      <phone>Please Email</phone>
      <email>Clinical.Trials@bms.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/NCT03755518
org study id: FEDR-MF-001
secondary id: U1111-1223-2862
secondary id: 2018-002237-38
nct id: NCT03755518
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS
      (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary
      Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential
      Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

      The primary objective of the study is to evaluate the percentage of subjects with at least a
      35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of
      fedratinib.
This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS
      (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary
      Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential
      Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

      The spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary
      objectives of the study are to further evaluate the safety and to assess and implement
      mitigation strategies for WE and for gastrointestinal (GI) adverse events.

      The study will be at multiple centers to provide access to a broad population and have
      assurance the results are likely to have general applicability.

      This is also conducted as an open-label study to collect efficacy and safety data with
      fedratinib use, no randomization or stratification will occur.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs
time frame: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 128 weeks)
description: Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.
measure: Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs
time frame: From first dose up to 30 days post last dose. (an average of 50.3 weeks up to a maximum of 124 weeks)
description: Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.
measure: Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in hematology laboratory analysis - hemoglobin
measure: Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in hematology laboratory analysis - erythrocytes.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in hematology laboratory analysis - blasts/leukocytes
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine
time frame: at Cycle 4 Day 1 and Cycle 7 Day 1
description: Mean change from baseline in chemistry parameters analysis - Creatinine.
Baseline value is defined as the last value or measurement taken prior to the first dose in the study
measure: Spleen Response Rate by Palpation
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.
measure: Symptom Response Rate
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS > 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.
measure: Durability of Spleen Volume Response by MRI/CT (DR)
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction < 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.
measure: Durability of Spleen Response by Palpation (DRP)
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.
measure: Durability of Symptom Response (DSR)
time frame: From First Dose to end of Cycle 6 (approximately 168 days)
description: Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction < 50%. In the absence of TSS reduction < 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.
measure: Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.
time frame: From first dose to end of treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
description: Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.
measure: Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN).
time frame: At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
description: Number of participants with thiamine levels < LLN.
LLN of thiamine is 70 nmol/L.
measure: Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN).
time frame: At Screening, Cycle 1, 2, 3, 6, 9, 15, 18, 21, 24, 27, 30 and End of Treatment (an average of 50.3 weeks up to a maximum of 124 weeks)
description: Number of participants with thiamine levels > ULN.
ULN of thiamine is 180 nmol/L.
arm group label: Administration of Fedratinib 400mg/day
arm group type: Experimental
description: Self-administered Investigational Product (IP) (400 mg/day) on an outpatient basis, once daily preferably with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.
intervention type: Drug
intervention name: FEDRATINIB
description: A potent and selective inhibitor of JAK2 kinase activity
arm group label: Administration of Fedratinib 400mg/day
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
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country: Canada
country: United States
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
url: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
description: FDA Safety Alerts and Recalls
responsible party type: Sponsor
mesh term: Polycythemia Vera
mesh term: Primary Myelofibrosis
mesh term: Polycythemia
mesh term: Thrombocytosis
mesh term: Thrombocythemia, Essential
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 