<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/NCT01727336</url>
  </required_header>
  <id_info>
    <org_study_id>A041-04</org_study_id>
    <secondary_id>ACE-041</secondary_id>
    <nct_id>NCT01727336</nct_id>
  </id_info>
  <brief_title>Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma</brief_title>
  <official_title>A Phase 2 Randomized, Double-Blind Study of Dalantercept and Axitinib Compared to Placebo and Axitinib in Patients With Advanced Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck &amp; Co., Inc., Rahway, NJ USA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck &amp; Co., Inc., Rahway, NJ USA</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of Part 1 of this study is to evaluate the safety and tolerability of&#xD;
      dalantercept in combination with axitinib in patients with advanced renal cell carcinoma&#xD;
      (RCC) to determine the recommended dose level of dalantercept in combination with axitinib&#xD;
      for Part 2.&#xD;
&#xD;
      The purpose of Part 2 of this study is to determine whether treatment with dalantercept in&#xD;
      combination with axitinib prolongs progression free survival (PFS) compared to axitinib alone&#xD;
      in patients with advanced renal cell carcinoma (RCC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Part 1 of the study, groups of subjects received escalating doses of dalantercept; 0.6,&#xD;
      0.9 and 1.2 mg/kg in sequential groups. All subjects received concurrent axitinib 5 mg PO&#xD;
      BID. A total of 29 subjects were enrolled i Part 1 of the study.&#xD;
&#xD;
      In Part 2, dalantercept at 0.9 mg/kg once every 3 weeks plus axitinib 5 mg PO BID was&#xD;
      compared to placebo plus axitinib 5 mg PO BID. A total of 131 subjects were enrolled in Part&#xD;
      2 for a total of 160 in the study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminated by the sponsor following unblinding of the Progression Free Survival&#xD;
    endpoint.&#xD;
  </why_stopped>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Part 1 of the study involved a dose escalation phase to select a dose for Part 2 of the study. In Part 1, a total of 29 subjects escalated through 3 dose levels of dalantercept: 0.6, 0.9 and 1.2 mg/kg once every 3 weeks. In Part 2, dalantercept (0.9 mg/kg once every 3 weeks) plus axitinib 5 mg PO BID) was compared with placebo plus axitinib 5 mg PO BID. Part 2 enrolled 131 subjects for a total of 160 subjects in the study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability.</measure>
    <time_frame>Assessed from time of first dose to approximately 30 days after last dose. Participants were allowed to remain on treatment until documented disease progression. The time frame for Part 1 of the study was up to 21.6 months</time_frame>
    <description>Outcome measure is intended for Part 1 of the study in order to determine recommended dose level for Part 2.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Progression Free Survival (PFS).</measure>
    <time_frame>Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months</time_frame>
    <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.&#xD;
RECIST 1.1 defines disease progression as an increase of at least a 20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: Progression Free Survival (PFS).</measure>
    <time_frame>The time frame for Part 1 of the study was up to 21.6 months</time_frame>
    <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Overall Survival (OS). [The Time Frame for Part 1 of the Study Was up to 21.6 Months]</measure>
    <time_frame>Up to 21.6 months</time_frame>
    <description>Percentage of Part 1 subjects alive at the end of Part 1 of the study. [The time frame for Part 1 of the study was up to 21.6 months]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Objective Response Rate (ORR)</measure>
    <time_frame>Up to 21.6 months from randomization in Part 1 of the study</time_frame>
    <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As no subjects in Part 1 experienced a CR, the ORR in Part 1 is defined by the PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Disease Control Rate (DCR)</measure>
    <time_frame>From randomization up to 21.6 months in Part 1 of the study</time_frame>
    <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Duration of Response (DoR)</measure>
    <time_frame>From randomization up to 21.6 months in Part 1 of the study.</time_frame>
    <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Progression Free Survival (PFS) for the Subset of Participants With 2 or More Lines of Prior Systemic Chemotherapy</measure>
    <time_frame>Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months</time_frame>
    <description>Progression Free Survival (PFS) for the subset of participants with 2 or more lines of prior systemic chemotherapy. PFS was based upon RECIST 1.1 assessment, as described in outcome measure 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Overall Survival.</measure>
    <time_frame>Patients to be contacted every 3 months for up to 12 months (anticipated) for survival follow-up, as well as tumor assessment scans if progression of disease has not previously been documented. The time frame for Part 2 was up to 29.0 months</time_frame>
    <description>The number of months from the date of randomization to the date of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Objective Response Rate.</measure>
    <time_frame>Assessed at 30 days after last dose of study drug; up to 29.0 months for Part 2 of the study</time_frame>
    <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Duration of Response</measure>
    <time_frame>Assessed at 30 days after the last dose of study drug; up to 29.0 months for Part 2 of the study.</time_frame>
    <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Disease Control Rate.</measure>
    <time_frame>Assessed at 30 days after last dose of study drug. The time frame for Part 2 was up to 29.0 months</time_frame>
    <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Part 1: Exploratory PD - Serum BMP9</measure>
    <time_frame>From randomization up to 21.6 months in Part 1 of the study</time_frame>
    <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
  </other_outcome>
  <other_outcome>
    <measure>Part 2: PD Biomarker Activities.</measure>
    <time_frame>Assessed at 30 days after the last dose of dalantercept ± 10 days. The time frame for Part 2 was up to 29.0 months.</time_frame>
    <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Advanced Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Dalantercept 0.9 mg/kg plus axitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous (SC) injection of dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus axitinib</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dalantercept 0.6 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose escalation arm 0.6 mg/kg dalantercept once every 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dalantercept 0.9 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose escalation arm 0.9 mg/kg dalantercept once every 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dalantercept 1.2 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose escalation arm 1.2 mg/kg dalantercept once every 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dalantercept 1.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1 dose escalation arm 1.5 mg/kg dalantercept once every 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dalantercept and axitinib</intervention_name>
    <arm_group_label>Dalantercept 0.6 mg/kg</arm_group_label>
    <arm_group_label>Dalantercept 0.9 mg/kg</arm_group_label>
    <arm_group_label>Dalantercept 0.9 mg/kg plus axitinib</arm_group_label>
    <arm_group_label>Dalantercept 1.2 mg/kg</arm_group_label>
    <arm_group_label>Dalantercept 1.5 mg/kg</arm_group_label>
    <other_name>ACE-041, Inlyta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo and axitinib</intervention_name>
    <arm_group_label>Placebo plus axitinib</arm_group_label>
    <other_name>Inlyta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed, advanced, predominantly clear cell renal cell carcinoma&#xD;
             (RCC).&#xD;
&#xD;
          -  Part 1: Progression of disease following up to three lines of prior therapy, including&#xD;
             at least one approved VEGF receptor tyrosine kinase inhibitor for RCC. Adjuvant&#xD;
             therapy is permitted as one line of prior therapy.&#xD;
&#xD;
          -  Part 2: Progression of disease following one VEGF pathway inhibitor for RCC (e.g.&#xD;
             sunitinib, pazopanib, sorafenib, bevacizumab, tivozanib, or cabozantinib) inclusive of&#xD;
             adjuvant therapy if there was documented disease progression during treatment.&#xD;
             Patients may have received one additional line of an approved mTOR kinase inhibitor&#xD;
             (e.g. everolimus, temsirolimus). Prior exposure to investigational and/or approved&#xD;
             anticancer immune therapies is permitted.&#xD;
&#xD;
          -  A minimum of 1 week since the last dose of prior therapy (a minimum of 4 weeks since&#xD;
             anticancer immune therapy or bevacizumab +/- interferon).&#xD;
&#xD;
          -  Measurable disease that is evaluable by Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) v1.1.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks.&#xD;
&#xD;
          -  Clinical laboratory values within acceptable ranges within 72 hours prior to study day&#xD;
             1.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant organ/system disease unrelated to RCC that in the judgment of&#xD;
             the investigator should preclude treatment with dalantercept or axitinib.&#xD;
&#xD;
          -  Clinically significant cardiovascular risk.&#xD;
&#xD;
          -  Known CNS metastases or leptomeningeal disease:&#xD;
&#xD;
        For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma&#xD;
        knife, and/or surgery who are considered stable by CNS imaging and are not being treated&#xD;
        with corticosteroids 6 weeks prior to study day 1 may be enrolled.&#xD;
&#xD;
        For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or&#xD;
        surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment&#xD;
        and are not being treated with corticosteroids 6 weeks prior to study day 1 may be&#xD;
        enrolled.&#xD;
&#xD;
          -  Any active malignancy, other than RCC, for which chemotherapy or other anti-cancer&#xD;
             therapy is indicated. Patients with adequately treated non-melanoma skin cancer, in&#xD;
             situ cancer, or other cancer from which the subject has been disease-free for at least&#xD;
             3 years will be permitted.&#xD;
&#xD;
          -  Any lesion invading or having encasement ≥ 180 degrees around the wall of a major&#xD;
             blood vessel as assessed by computed tomography (CT) scan and/or magnetic resonance&#xD;
             imaging (MRI).&#xD;
&#xD;
          -  Radiotherapy within 2 weeks prior to study day 1.&#xD;
&#xD;
          -  Lack of recovery from toxic effects of previous treatment for RCC ≤ grade 1 with the&#xD;
             exception of alopecia, unless stabilized under adequate medical control.&#xD;
&#xD;
          -  Patients undergoing renal dialysis.&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to study day 1 (patients must have recovered&#xD;
             completely from any previous surgery prior to study day 1).&#xD;
&#xD;
          -  Any active infection requiring antibiotic therapy within 2 weeks of study day 1.&#xD;
&#xD;
          -  Anti-coagulation therapy. Aspirin, other anti-platelet agents, and low molecular&#xD;
             weight heparin are permitted unless the investigator deems the patient is at a&#xD;
             significant risk for bleeding.&#xD;
&#xD;
          -  Current use or anticipated inability to avoid potent CYP3A4/5 inhibitors or inducers&#xD;
             (please refer to the Inlyta® [axitinib] prescribing information) during participation&#xD;
             in the study.&#xD;
&#xD;
          -  Peripheral edema requiring medical intervention within 2 weeks prior to study day 1.&#xD;
&#xD;
          -  Bleeding diathesis including clinically significant platelet disorders or active&#xD;
             hemoptysis (defined as bright red blood of ≥ 1/2 teaspoon [2.5 mL] in any 24 hour&#xD;
             period) within 6 months prior to study day 1. For clinically significant epistaxis&#xD;
             within 4 weeks prior to study day 1, no risk of further bleeding must be clearly&#xD;
             documented.&#xD;
&#xD;
          -  Known history of hereditary hemorrhagic telangiectasia (HHT).&#xD;
&#xD;
          -  Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or positive&#xD;
             human immunodeficiency virus (HIV) antibody results. Patients with sustained virologic&#xD;
             response to HCV treatment or immunity to HBV from prior infection without cirrhosis&#xD;
             may be included.&#xD;
&#xD;
          -  History of severe (defined as ≥ grade 3, using the National Cancer Institute Common&#xD;
             Toxicity Criteria for Adverse Events, version 4.0 [NCI-CTCAE] v4 current active minor&#xD;
             version) allergic or anaphylactic reaction or hypersensitivity to recombinant proteins&#xD;
             or excipients (10 mM Tris buffered saline) in the investigational agent.&#xD;
&#xD;
          -  Any prior treatment with dalantercept or any other agent targeting ALK1 pathway.&#xD;
&#xD;
          -  Any prior treatment with axitinib.&#xD;
&#xD;
          -  A morbidity (per the prescribing information) that would require starting a patient at&#xD;
             a reduced dose of axitinib.&#xD;
&#xD;
          -  Treatment with another investigational drug (with the exception of anticancer immune&#xD;
             therapy) or device, or approved therapy for investigational use, within 5 times the&#xD;
             half-life of the drug or within 3 weeks prior to study day 1 if the half life is not&#xD;
             known.&#xD;
&#xD;
          -  Pregnant or lactating female patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Oncology Associates, PC - HOPE</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Highlands Oncology Group, PA</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Irvine Medical Center</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92697</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles (UCLA) - Institute of Urologic Oncology</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Hospital and Clinics</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Health Melvin &amp; Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Med Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital &amp; Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Methodist Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center Hackensack UMC</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology, P.C.</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore LIJ Center for Advance Medicine</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mem Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Cancer Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levin Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C.</name>
      <address>
        <city>Tualatin</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's University Health Network</name>
      <address>
        <city>Bethlehem</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S- Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh, Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-South Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-El Paso Cancer Treatment Center Grandview</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Memorial City</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Tyler and Longview</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shenandoah Oncology P.C.</name>
      <address>
        <city>Winchester</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin, Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <results_first_submitted>April 28, 2021</results_first_submitted>
  <results_first_submitted_qc>May 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 24, 2021</results_first_posted>
  <last_update_submitted>September 12, 2022</last_update_submitted>
  <last_update_submitted_qc>September 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Axitinib</mesh_term>
  </intervention_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>June 19, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT01727336/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>In the Part 1 dose escalation portion of the study, 4 dose levels of dalantercept plus an expansion cohort were planned. However, dose escalation was suspended following the 1.2 mg/kg dose level and additional subjects were added to the 1.2 mg/kg dose cohort, which represented the expansion; no subjects were enrolled in the 1.5 mg/kg dose level.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1 Dalantercept 0.6 mg/kg</title>
          <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="P2">
          <title>Part 1 Dalantercept 0.9 mg/kg</title>
          <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="P3">
          <title>Part 1: Dalantercept 1.2 mg/kg</title>
          <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="P4">
          <title>Part 1: Dalantercept 1.5 mg/kg</title>
          <description>Dose escalation cohort 4: dalantercept 1.5 mg/kg</description>
        </group>
        <group group_id="P5">
          <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
          <description>Subcutaneous (SC) injection of Dalantercept once every 3 weeks and oral axitinib 5 mg PO BID for continuous dosing.</description>
        </group>
        <group group_id="P6">
          <title>Part 2: Placebo Plus Axitinib</title>
          <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg PO BID for continuous dosing</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1 Dalantercept Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2 Blinded</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="63"/>
                <participants group_id="P6" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="63"/>
                <participants group_id="P6" count="68"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="20"/>
                <participants group_id="P6" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="42"/>
                <participants group_id="P6" count="44"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>use of prohibited medications</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No subjects were enrolled into the 1.5 mg/kg dose escalation cohort</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1 Dalantercept 0.6 mg/kg</title>
          <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg</description>
        </group>
        <group group_id="B2">
          <title>Part 1 Dalantercept 0.9 mg/kg</title>
          <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg</description>
        </group>
        <group group_id="B3">
          <title>Part 1 Dalantercept 1.2 mg/kg</title>
          <description>Dose escalation cohort 3: dalantercept 1.2 mg/kg</description>
        </group>
        <group group_id="B4">
          <title>Part 1 Dalantercept 1.5 mg/kg</title>
          <description>Dose escalation cohort 4: dalantercept 1.5 mg/kg</description>
        </group>
        <group group_id="B5">
          <title>Part 2 Dalantercept 0.9 mg/kg Plus Axitinib</title>
          <description>Subcutaneous (SC) injection of Dalantercept once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
        </group>
        <group group_id="B6">
          <title>Placebo Plus Axitinib</title>
          <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="14"/>
            <count group_id="B4" value="0"/>
            <count group_id="B5" value="63"/>
            <count group_id="B6" value="68"/>
            <count group_id="B7" value="160"/>
          </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="64.3" spread="7.2"/>
                    <measurement group_id="B2" value="56.2" spread="9.2"/>
                    <measurement group_id="B3" value="61.5" spread="10.9"/>
                    <measurement group_id="B5" value="62.8" spread="8.1"/>
                    <measurement group_id="B6" value="58.9" spread="10.1"/>
                    <measurement group_id="B7" value="60.7" spread="9.4"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B5" value="22"/>
                    <measurement group_id="B6" value="28"/>
                    <measurement group_id="B7" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B5" value="41"/>
                    <measurement group_id="B6" value="40"/>
                    <measurement group_id="B7" value="104"/>
                  </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 group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B5" value="58"/>
                    <measurement group_id="B6" value="58"/>
                    <measurement group_id="B7" value="143"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B5" value="63"/>
                    <measurement group_id="B6" value="68"/>
                    <measurement group_id="B7" value="160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability.</title>
        <description>Outcome measure is intended for Part 1 of the study in order to determine recommended dose level for Part 2.</description>
        <time_frame>Assessed from time of first dose to approximately 30 days after last dose. Participants were allowed to remain on treatment until documented disease progression. The time frame for Part 1 of the study was up to 21.6 months</time_frame>
        <population>Safety Analysis Set (SAF) consisted of all patients who received at least 1 dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Part 1 cohort 1; dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Part 1 cohort 2; dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1 Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3; dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O4">
            <title>Part 1 Dalantercept 1.5 mg/kg</title>
            <description>Part 1 cohort 1; dalantercept 1.5 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability.</title>
          <description>Outcome measure is intended for Part 1 of the study in order to determine recommended dose level for Part 2.</description>
          <population>Safety Analysis Set (SAF) consisted of all patients who received at least 1 dose of study drug</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="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>recommended dose for Part 2</param_type>
            <param_value>0.9</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The recommended dose level for Part 2 was determined to be 0.9 mg/kg</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part 2: Progression Free Survival (PFS).</title>
        <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.&#xD;
RECIST 1.1 defines disease progression as an increase of at least a 20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression)</description>
        <time_frame>Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months</time_frame>
        <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Progression Free Survival (PFS).</title>
          <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.&#xD;
RECIST 1.1 defines disease progression as an increase of at least a 20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression)</description>
          <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
          <units>Months</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="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" lower_limit="4.5" upper_limit="9.4"/>
                    <measurement group_id="O2" value="5.6" lower_limit="3.3" upper_limit="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Progression Free Survival (PFS).</title>
        <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
        <time_frame>The time frame for Part 1 of the study was up to 21.6 months</time_frame>
        <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Progression Free Survival (PFS).</title>
          <description>PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
          <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
          <units>Months</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="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" lower_limit="1.3" upper_limit="20.6"/>
                    <measurement group_id="O2" value="21.6" lower_limit="2.8" upper_limit="21.6"/>
                    <measurement group_id="O3" value="6.9" lower_limit="2.7" upper_limit="20.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Overall Survival (OS). [The Time Frame for Part 1 of the Study Was up to 21.6 Months]</title>
        <description>Percentage of Part 1 subjects alive at the end of Part 1 of the study. [The time frame for Part 1 of the study was up to 21.6 months]</description>
        <time_frame>Up to 21.6 months</time_frame>
        <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Overall Survival (OS). [The Time Frame for Part 1 of the Study Was up to 21.6 Months]</title>
          <description>Percentage of Part 1 subjects alive at the end of Part 1 of the study. [The time frame for Part 1 of the study was up to 21.6 months]</description>
          <population>Full Analysis Set; all subjects randomized in Part 1 of the study</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="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Objective Response Rate (ORR)</title>
        <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As no subjects in Part 1 experienced a CR, the ORR in Part 1 is defined by the PR</description>
        <time_frame>Up to 21.6 months from randomization in Part 1 of the study</time_frame>
        <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Objective Response Rate (ORR)</title>
          <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As no subjects in Part 1 experienced a CR, the ORR in Part 1 is defined by the PR</description>
          <population>Full Analysis Set; all subjects randomized in Part 1 of the study</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="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Disease Control Rate (DCR)</title>
        <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
        <time_frame>From randomization up to 21.6 months in Part 1 of the study</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Disease Control Rate (DCR)</title>
          <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: Duration of Response (DoR)</title>
        <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
        <time_frame>From randomization up to 21.6 months in Part 1 of the study.</time_frame>
        <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Dalantercept 0.6 mg/kg</title>
            <description>Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O2">
            <title>Part 1 Dalantercept 0.9 mg/kg</title>
            <description>Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Dalantercept 1.2 mg/kg</title>
            <description>Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Duration of Response (DoR)</title>
          <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
          <population>Full Analysis Set; all subjects randomized in Part 1 of the study</population>
          <units>months</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="6"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2.8" upper_limit="21.6"/>
                    <measurement group_id="O2" value="6.9" lower_limit="6.9" upper_limit="21.6"/>
                    <measurement group_id="O3" value="10" lower_limit="8.8" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Progression Free Survival (PFS) for the Subset of Participants With 2 or More Lines of Prior Systemic Chemotherapy</title>
        <description>Progression Free Survival (PFS) for the subset of participants with 2 or more lines of prior systemic chemotherapy. PFS was based upon RECIST 1.1 assessment, as described in outcome measure 2.</description>
        <time_frame>Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months</time_frame>
        <population>Subgroup of Part 2 participants:&#xD;
24 of 63 participants in the dalantercept arm and 22 of 68 participants in the placebo arm had at least 2 lines of prior systemic chemotherapy</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Progression Free Survival (PFS) for the Subset of Participants With 2 or More Lines of Prior Systemic Chemotherapy</title>
          <description>Progression Free Survival (PFS) for the subset of participants with 2 or more lines of prior systemic chemotherapy. PFS was based upon RECIST 1.1 assessment, as described in outcome measure 2.</description>
          <population>Subgroup of Part 2 participants:&#xD;
24 of 63 participants in the dalantercept arm and 22 of 68 participants in the placebo arm had at least 2 lines of prior systemic chemotherapy</population>
          <units>Months</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="24"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" lower_limit="3.6" upper_limit="10.5"/>
                    <measurement group_id="O2" value="7.0" lower_limit="2.8" upper_limit="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Overall Survival.</title>
        <description>The number of months from the date of randomization to the date of death.</description>
        <time_frame>Patients to be contacted every 3 months for up to 12 months (anticipated) for survival follow-up, as well as tumor assessment scans if progression of disease has not previously been documented. The time frame for Part 2 was up to 29.0 months</time_frame>
        <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Overall Survival.</title>
          <description>The number of months from the date of randomization to the date of death.</description>
          <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" lower_limit="9.3" upper_limit="14.5"/>
                    <measurement group_id="O2" value="14.7" lower_limit="7.3" upper_limit="20.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Objective Response Rate.</title>
        <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Assessed at 30 days after last dose of study drug; up to 29.0 months for Part 2 of the study</time_frame>
        <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Objective Response Rate.</title>
          <description>Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>The All Treated Set (ATS) included all randomized patients who received any study drug</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="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Duration of Response</title>
        <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
        <time_frame>Assessed at 30 days after the last dose of study drug; up to 29.0 months for Part 2 of the study.</time_frame>
        <population>The All Treatment Set (ATS) included all randomized patients who received any study drug. Please see Outcome Measure 5 for Objective Response Rate data. Since there were too few participants with events, an estimation of response duration was not able to be calculated due to the early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Duration of Response</title>
          <description>Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.</description>
          <population>The All Treatment Set (ATS) included all randomized patients who received any study drug. Please see Outcome Measure 5 for Objective Response Rate data. Since there were too few participants with events, an estimation of response duration was not able to be calculated due to the early termination of the study.</population>
          <units>Months</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="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">too few participants with events were available for an estimation of response duration due to the early termination of the study</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">too few participants with events were available for an estimation of response duration due to the early termination of the study</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Disease Control Rate.</title>
        <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
        <time_frame>Assessed at 30 days after last dose of study drug. The time frame for Part 2 was up to 29.0 months</time_frame>
        <population>The All Treated Set (ATS) included all randomized patients who received any study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Disease Control Rate.</title>
          <description>The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.</description>
          <population>The All Treated Set (ATS) included all randomized patients who received any study drug</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="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                    <measurement group_id="O2" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Part 1: Exploratory PD - Serum BMP9</title>
        <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
        <time_frame>From randomization up to 21.6 months in Part 1 of the study</time_frame>
        <population>All subjects randomized to Part 1 of the study and treated with at least 1 dose of dalantercept. Given the high degree of variability in serum BMP9 levels in study subjects [Baseline value 23.55 ng/mL (SD 20.54 ng/mL)] and the relative small numbers of subjects in each treatment arm, it was decided that the best way to understand a treatment effect was to conduct a pooled analysis of all 29 Part 1 subjects for the comparison of change from Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1 Participants</title>
            <description>Pooled number of Part 1 participants across the dose escalation groups 0.6 mg/kg (N=6), 0.9 mg/kg (N=9) and 1.2 mg/kg (N=14); total N=29 subjects</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Exploratory PD - Serum BMP9</title>
          <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
          <population>All subjects randomized to Part 1 of the study and treated with at least 1 dose of dalantercept. Given the high degree of variability in serum BMP9 levels in study subjects [Baseline value 23.55 ng/mL (SD 20.54 ng/mL)] and the relative small numbers of subjects in each treatment arm, it was decided that the best way to understand a treatment effect was to conduct a pooled analysis of all 29 Part 1 subjects for the comparison of change from Baseline.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.5" spread="2.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Part 2: PD Biomarker Activities.</title>
        <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
        <time_frame>Assessed at 30 days after the last dose of dalantercept ± 10 days. The time frame for Part 2 was up to 29.0 months.</time_frame>
        <population>The All Treated Set (ATS) included all randomized patients who received any study drug, and for whom sufficient blood sample was available to assess the exploratory biomarker.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
            <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo Plus Axitinib</title>
            <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: PD Biomarker Activities.</title>
          <description>Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)</description>
          <population>The All Treated Set (ATS) included all randomized patients who received any study drug, and for whom sufficient blood sample was available to assess the exploratory biomarker.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-53.34" spread="37.87"/>
                    <measurement group_id="O2" value="8.55" spread="86.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the initial study drug administration on Cycle 1, Day 1 (C1D1) until 30 days after the last study drug administration for each subject on study, up to a total of 29.0 months of study drug exposure</time_frame>
      <desc>Analyses of adverse events were carried out on the Safety Analysis Set, defined as all participants who received at least one dose of study drug.&#xD;
There were no subjects enrolled in Part 1 cohort 4 (1.5 mg/kg dalantercept), thus no subjects were at risk for adverse events</desc>
      <group_list>
        <group group_id="E1">
          <title>Part 1: Dalantercept 0.6 mg/kg</title>
          <description>Part 1 cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="E2">
          <title>Part 1: Dalantercept 0.9 mg/kg</title>
          <description>Part 1 cohort 1: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="E3">
          <title>Part 1: Dalantercept 1.2 mg/kg</title>
          <description>Part 1 cohort 1: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="E4">
          <title>Part 1: Dalantercept 1.5 mg/kg</title>
          <description>Part 1 cohort 1: dalantercept 1.5 mg/kg plus axitinib 5 mg PO BID</description>
        </group>
        <group group_id="E5">
          <title>Part 2: Dalantercept 0.9 mg/kg Plus Axitinib</title>
          <description>Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.</description>
        </group>
        <group group_id="E6">
          <title>Part 2: Placebo Plus Axitinib</title>
          <description>Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI CTCAE</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="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="20" subjects_at_risk="63"/>
                <counts group_id="E6" subjects_affected="16" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="19" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="16" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Anal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Obstruction gastric</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pancreatitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Transaminase increase</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Gate disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Periportal oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Anorectal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Soft tissue injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hodgkin's disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Tumour thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>PLeural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>NCI CTCAE</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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="61" subjects_at_risk="62"/>
                <counts group_id="E6" subjects_affected="64" subjects_at_risk="64"/>
              </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="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="13" subjects_affected="13" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="8" subjects_affected="8" subjects_at_risk="62"/>
                <counts group_id="E6" events="12" subjects_affected="12" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="54" subjects_affected="54" subjects_at_risk="62"/>
                <counts group_id="E6" events="55" subjects_affected="55" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="38" subjects_affected="38" subjects_at_risk="62"/>
                <counts group_id="E6" events="40" subjects_affected="40" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="24" subjects_affected="24" subjects_at_risk="62"/>
                <counts group_id="E6" events="28" subjects_affected="28" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="18" subjects_affected="18" subjects_at_risk="62"/>
                <counts group_id="E6" events="18" subjects_affected="18" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="13" subjects_affected="13" subjects_at_risk="62"/>
                <counts group_id="E6" events="16" subjects_affected="16" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="8" subjects_affected="8" subjects_at_risk="62"/>
                <counts group_id="E6" events="15" subjects_affected="15" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_at_risk="0"/>
                <counts group_id="E5" events="35" subjects_affected="35" subjects_at_risk="62"/>
                <counts group_id="E6" events="47" subjects_affected="47" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="8" subjects_affected="8" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="24" subjects_affected="24" subjects_at_risk="62"/>
                <counts group_id="E6" events="14" subjects_affected="14" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="13" subjects_affected="13" subjects_at_risk="62"/>
                <counts group_id="E6" events="20" subjects_affected="20" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="21" subjects_affected="21" subjects_at_risk="62"/>
                <counts group_id="E6" events="11" subjects_affected="11" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="9" subjects_affected="9" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="64"/>
              </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="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="23" subjects_affected="23" subjects_at_risk="62"/>
                <counts group_id="E6" events="20" subjects_affected="20" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="62"/>
                <counts group_id="E6" events="13" subjects_affected="13" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </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="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_at_risk="0"/>
                <counts group_id="E5" events="17" subjects_affected="17" subjects_at_risk="62"/>
                <counts group_id="E6" events="19" subjects_affected="19" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="10" subjects_affected="10" subjects_at_risk="62"/>
                <counts group_id="E6" events="14" subjects_affected="14" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="14" subjects_affected="14" subjects_at_risk="62"/>
                <counts group_id="E6" events="9" subjects_affected="9" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="10" subjects_affected="10" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="9" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="14" subjects_affected="14" subjects_at_risk="62"/>
                <counts group_id="E6" events="21" subjects_affected="21" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="9" subjects_affected="9" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="11" subjects_affected="11" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="9" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="11" subjects_affected="11" subjects_at_risk="62"/>
                <counts group_id="E6" events="25" subjects_affected="25" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="24" subjects_affected="24" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="16" subjects_affected="16" subjects_at_risk="62"/>
                <counts group_id="E6" events="13" subjects_affected="13" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="15" subjects_affected="15" subjects_at_risk="62"/>
                <counts group_id="E6" events="15" subjects_affected="15" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E6" events="12" subjects_affected="12" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="8" subjects_affected="8" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="13" subjects_affected="13" subjects_at_risk="62"/>
                <counts group_id="E6" events="30" subjects_affected="30" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>All 131 patients in Part 2 discontinued from the study; the most frequent reasons were (i) study terminated at the discretion of the sponsor [86 patients (65.6%)] and (ii) death [36 patients (27.5%)]. The discontinuations prior to planned sample collections, as outlined in the protocol schedule of events, precluded the ability to carry out all planned analyses, including but not limited to PK analyses. Dalantercept PK in patients with advanced cancer has been reported previously.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT01727336
org study id: A041-04
secondary id: ACE-041
nct id: NCT01727336
lead sponsor: 
has dmc: Yes
The purpose of Part 1 of this study is to evaluate the safety and tolerability of
      dalantercept in combination with axitinib in patients with advanced renal cell carcinoma
      (RCC) to determine the recommended dose level of dalantercept in combination with axitinib
      for Part 2.

      The purpose of Part 2 of this study is to determine whether treatment with dalantercept in
      combination with axitinib prolongs progression free survival (PFS) compared to axitinib alone
      in patients with advanced renal cell carcinoma (RCC).
In Part 1 of the study, groups of subjects received escalating doses of dalantercept; 0.6,
      0.9 and 1.2 mg/kg in sequential groups. All subjects received concurrent axitinib 5 mg PO
      BID. A total of 29 subjects were enrolled i Part 1 of the study.

      In Part 2, dalantercept at 0.9 mg/kg once every 3 weeks plus axitinib 5 mg PO BID was
      compared to placebo plus axitinib 5 mg PO BID. A total of 131 subjects were enrolled in Part
      2 for a total of 160 in the study
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Part 1 of the study involved a dose escalation phase to select a dose for Part 2 of the study. In Part 1, a total of 29 subjects escalated through 3 dose levels of dalantercept: 0.6, 0.9 and 1.2 mg/kg once every 3 weeks. In Part 2, dalantercept (0.9 mg/kg once every 3 weeks) plus axitinib 5 mg PO BID) was compared with placebo plus axitinib 5 mg PO BID. Part 2 enrolled 131 subjects for a total of 160 subjects in the study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability.
time frame: Assessed from time of first dose to approximately 30 days after last dose. Participants were allowed to remain on treatment until documented disease progression. The time frame for Part 1 of the study was up to 21.6 months
description: Outcome measure is intended for Part 1 of the study in order to determine recommended dose level for Part 2.
measure: Part 2: Progression Free Survival (PFS).
time frame: Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months
description: PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
RECIST 1.1 defines disease progression as an increase of at least a 20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression)
measure: Part 1: Progression Free Survival (PFS).
time frame: The time frame for Part 1 of the study was up to 21.6 months
description: PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
measure: Part 1: Overall Survival (OS). [The Time Frame for Part 1 of the Study Was up to 21.6 Months]
time frame: Up to 21.6 months
description: Percentage of Part 1 subjects alive at the end of Part 1 of the study. [The time frame for Part 1 of the study was up to 21.6 months]
measure: Part 1: Objective Response Rate (ORR)
time frame: Up to 21.6 months from randomization in Part 1 of the study
description: Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As no subjects in Part 1 experienced a CR, the ORR in Part 1 is defined by the PR
measure: Part 1: Disease Control Rate (DCR)
time frame: From randomization up to 21.6 months in Part 1 of the study
description: The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.
measure: Part 1: Duration of Response (DoR)
time frame: From randomization up to 21.6 months in Part 1 of the study.
description: Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.
measure: Part 2: Progression Free Survival (PFS) for the Subset of Participants With 2 or More Lines of Prior Systemic Chemotherapy
time frame: Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months
description: Progression Free Survival (PFS) for the subset of participants with 2 or more lines of prior systemic chemotherapy. PFS was based upon RECIST 1.1 assessment, as described in outcome measure 2.
measure: Part 2: Overall Survival.
time frame: Patients to be contacted every 3 months for up to 12 months (anticipated) for survival follow-up, as well as tumor assessment scans if progression of disease has not previously been documented. The time frame for Part 2 was up to 29.0 months
description: The number of months from the date of randomization to the date of death.
measure: Part 2: Objective Response Rate.
time frame: Assessed at 30 days after last dose of study drug; up to 29.0 months for Part 2 of the study
description: Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Part 2: Duration of Response
time frame: Assessed at 30 days after the last dose of study drug; up to 29.0 months for Part 2 of the study.
description: Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.
measure: Part 2: Disease Control Rate.
time frame: Assessed at 30 days after last dose of study drug. The time frame for Part 2 was up to 29.0 months
description: The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.
measure: Part 1: Exploratory PD - Serum BMP9
time frame: From randomization up to 21.6 months in Part 1 of the study
description: Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)
measure: Part 2: PD Biomarker Activities.
time frame: Assessed at 30 days after the last dose of dalantercept ± 10 days. The time frame for Part 2 was up to 29.0 months.
description: Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)
arm group label: Dalantercept 0.9 mg/kg plus axitinib
arm group type: Experimental
description: Subcutaneous (SC) injection of dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.
arm group label: Placebo plus axitinib
arm group type: Placebo Comparator
description: Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
arm group label: Dalantercept 0.6 mg/kg
arm group type: Experimental
description: Part 1 dose escalation arm 0.6 mg/kg dalantercept once every 3 weeks
arm group label: Dalantercept 0.9 mg/kg
arm group type: Experimental
description: Part 1 dose escalation arm 0.9 mg/kg dalantercept once every 3 weeks
arm group label: Dalantercept 1.2 mg/kg
arm group type: Experimental
description: Part 1 dose escalation arm 1.2 mg/kg dalantercept once every 3 weeks
arm group label: Dalantercept 1.5 mg/kg
arm group type: Experimental
description: Part 1 dose escalation arm 1.5 mg/kg dalantercept once every 3 weeks
intervention type: Drug
intervention name: Dalantercept and axitinib
arm group label: Dalantercept 0.6 mg/kg
arm group label: Dalantercept 0.9 mg/kg
arm group label: Dalantercept 0.9 mg/kg plus axitinib
arm group label: Dalantercept 1.2 mg/kg
arm group label: Dalantercept 1.5 mg/kg
other name: ACE-041, Inlyta
intervention type: Drug
intervention name: Placebo and axitinib
arm group label: Placebo plus axitinib
other name: Inlyta
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Axitinib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: All 131 patients in Part 2 discontinued from the study; the most frequent reasons were (i) study terminated at the discretion of the sponsor [86 patients (65.6%)] and (ii) death [36 patients (27.5%)]. The discontinuations prior to planned sample collections, as outlined in the protocol schedule of events, precluded the ability to carry out all planned analyses, including but not limited to PK analyses. Dalantercept PK in patients with advanced cancer has been reported previously.
point of contact: 