<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/NCT01692366</url>
  </required_header>
  <id_info>
    <org_study_id>ARD12888</org_study_id>
    <secondary_id>U1111-1130-3710</secondary_id>
    <nct_id>NCT01692366</nct_id>
  </id_info>
  <brief_title>Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly</brief_title>
  <official_title>A Phase 2 Open-Label, Dose-Ranging Study of the Efficacy and Safety of Orally Administered SAR302503 in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      - To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 and&#xD;
      combined for the response rate defined with the ≥35% reduction of spleen volume as determined&#xD;
      by magnetic resonance imaging (MRI or computed tomography scan [CT] in patients with&#xD;
      contraindications for MRI).&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the safety of SAR302503 for both pooled (300, 400, and 500mg) and individual&#xD;
           doses population.&#xD;
&#xD;
        -  To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat-dose.&#xD;
&#xD;
        -  To evaluate the effect on Myelofibrosis (MF)-associated symptoms (Key MF symptoms) as&#xD;
           measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF).&#xD;
&#xD;
        -  To evaluate the durability of splenic response.&#xD;
&#xD;
        -  To evaluate the effect of SAR302503 on bone marrow with regard to changes on reticulin&#xD;
           fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The duration of the study for an individual patient will include a period to assess&#xD;
      eligibility (screening period 28 days), followed by a treatment period of at least 1 cycle&#xD;
      (28 days) of study treatment, and an end-of-treatment visit at least 30 days following the&#xD;
      last administration of study drug. However, treatment may continue if patients are deriving&#xD;
      benefit and do not have unacceptable toxicity or meet study withdrawal criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:</measure>
    <time_frame>24 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signs</measure>
    <time_frame>From baseline to the 30 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24</measure>
    <time_frame>SAR302503, pre-dose and post-dose plasma collections will be obtained on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 2, and Cycle 3 Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of maintenance of ≥35% reduction in spleen volume</measure>
    <time_frame>From baseline to the 30 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in spleen volume measured by MRI</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in spleen size measured by palpation</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with any grade reduction in reticulin fibrosis</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>SAR302503 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 300mg. SAR302503 will be taken on an empty stomach at approximately the same time each day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR302503 400 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR302503 500 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 500 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAR302503</intervention_name>
    <description>Pharmaceutical form:Capsule&#xD;
Route of administration: oral</description>
    <arm_group_label>SAR302503 300mg</arm_group_label>
    <arm_group_label>SAR302503 400 mg</arm_group_label>
    <arm_group_label>SAR302503 500 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia&#xD;
             myelofibrosis&#xD;
&#xD;
          -  Myelofibrosis classified as high-risk or intermediate-risk level 2&#xD;
&#xD;
          -  Enlarged spleen, palpable at least 5 cm below costal margin&#xD;
&#xD;
          -  Active symptoms of myelofibrosis&#xD;
&#xD;
          -  At least 20 years of age&#xD;
&#xD;
          -  Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at&#xD;
             study entry&#xD;
&#xD;
          -  Absence of active malignancy other than myelofibrosis&#xD;
&#xD;
          -  Written informed consent to participate.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Splenectomy.&#xD;
&#xD;
          -  Any recent chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg,&#xD;
             thalidomide, interferon-alpha), immunosuppressive therapy, corticosteroids &gt;10 mg/day&#xD;
             prednisone or equivalent, or growth factor treatment (eg, erythropoietin), hormones&#xD;
             (eg, androgens, danazol) within 14 days prior to initiation of study drug.&#xD;
&#xD;
          -  Major surgery therapy within 28 days or radiation including spleen radiation within 6&#xD;
             months prior to initiation of study drug.&#xD;
&#xD;
          -  Concomitant treatment with or use of pharmaceutical or herbal agents known to be&#xD;
             moderate or severe inhibitors or inducers CYP3A4.&#xD;
&#xD;
          -  Active acute infection requiring antibiotics.&#xD;
&#xD;
          -  Uncontrolled congestive heart failure (New York Heart Association Classification 3 or&#xD;
             4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral&#xD;
             artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3&#xD;
             months prior to initiation of study drug.&#xD;
&#xD;
          -  Participation in any study of an investigational agent (drug, biologic, device) within&#xD;
             30 days, unless during nontreatment phase.&#xD;
&#xD;
          -  Prior treatment with a JAK 2 Inhibitor.&#xD;
&#xD;
          -  Treatment with aspirin in doses &gt;150 mg/day&#xD;
&#xD;
          -  Known human immunodeficiency virus or acquired immunodeficiency syndrome-related&#xD;
             illness.&#xD;
&#xD;
          -  Pregnant or lactating female. Once the lactating female stop and participate in the&#xD;
             study, she cannot re-start feeding the baby.&#xD;
&#xD;
          -  Women of childbearing potential, unless using effective contraception while on study&#xD;
             drug. Otherwise patients must be post-menopausal (at least 1 years from last&#xD;
             menstruation without other medical reason), or surgically sterile.&#xD;
&#xD;
          -  Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers.&#xD;
&#xD;
          -  Prior history of chronic liver disease (eg, chronic alcoholic liver disease,&#xD;
             autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,&#xD;
             hemachromatosis, non-alcoholic steatohepatitis [NASH])&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 392010</name>
      <address>
        <city>Akita-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392002</name>
      <address>
        <city>Bunkyo-Ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392006</name>
      <address>
        <city>Bunkyo-Ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392004</name>
      <address>
        <city>Sendai-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392008</name>
      <address>
        <city>Shinjuku-Ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392009</name>
      <address>
        <city>Shinjuku-Ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 392003</name>
      <address>
        <city>Suita-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>September 19, 2014</last_update_submitted>
  <last_update_submitted_qc>September 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 22, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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>
    <mesh_term>Splenomegaly</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01692366
org study id: ARD12888
secondary id: U1111-1130-3710
nct id: NCT01692366
lead sponsor: 
has dmc: No
Primary Objective:

      - To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 and
      combined for the response rate defined with the ≥35% reduction of spleen volume as determined
      by magnetic resonance imaging (MRI or computed tomography scan [CT] in patients with
      contraindications for MRI).

      Secondary Objectives:

        -  To evaluate the safety of SAR302503 for both pooled (300, 400, and 500mg) and individual
           doses population.

        -  To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat-dose.

        -  To evaluate the effect on Myelofibrosis (MF)-associated symptoms (Key MF symptoms) as
           measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF).

        -  To evaluate the durability of splenic response.

        -  To evaluate the effect of SAR302503 on bone marrow with regard to changes on reticulin
           fibrosis.
The duration of the study for an individual patient will include a period to assess
      eligibility (screening period 28 days), followed by a treatment period of at least 1 cycle
      (28 days) of study treatment, and an end-of-treatment visit at least 30 days following the
      last administration of study drug. However, treatment may continue if patients are deriving
      benefit and do not have unacceptable toxicity or meet study withdrawal criteria.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:
time frame: 24 weeks
measure: Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signs
time frame: From baseline to the 30 days after last drug administration
measure: Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24
time frame: SAR302503, pre-dose and post-dose plasma collections will be obtained on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 2, and Cycle 3 Day 1
measure: Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF
time frame: 24 weeks
measure: Duration of maintenance of ≥35% reduction in spleen volume
time frame: From baseline to the 30 days after last drug administration
measure: Percent change from baseline in spleen volume measured by MRI
time frame: 24 weeks
measure: Percent change from baseline in spleen size measured by palpation
time frame: 24 weeks
measure: Proportion of patients with any grade reduction in reticulin fibrosis
time frame: 24 weeks
arm group label: SAR302503 300mg
arm group type: Experimental
description: SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 300mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
arm group label: SAR302503 400 mg
arm group type: Experimental
description: SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
arm group label: SAR302503 500 mg
arm group type: Experimental
description: SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 500 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
intervention type: Drug
intervention name: SAR302503
description: Pharmaceutical form:Capsule
Route of administration: oral
arm group label: SAR302503 300mg
arm group label: SAR302503 400 mg
arm group label: SAR302503 500 mg
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Polycythemia Vera
mesh term: Primary Myelofibrosis
mesh term: Polycythemia
mesh term: Thrombocytosis
mesh term: Thrombocythemia, Essential
mesh term: Splenomegaly