<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/NCT03033524</url>
  </required_header>
  <id_info>
    <org_study_id>PMC_TTAC-0001_02</org_study_id>
    <nct_id>NCT03033524</nct_id>
  </id_info>
  <brief_title>Trial to Evaluate the Safety of TTAC-0001(Tanibirumab) in Recurrent Glioblastoma</brief_title>
  <official_title>A Multicenter, 3-Arm, Open-Label, Phase Ⅱa Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001, a Fully Human Monoclonal Antibody in Patients With Recurrent Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PharmAbcine</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PharmAbcine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Design - Multicenter, open-label, 3 arms, stepwise, phase Ⅱa clinical trial&#xD;
&#xD;
      Study objective:&#xD;
&#xD;
        1. Primary - To evaluate the safety of TTAC-0001 in patients with recurrent glioblastoma.&#xD;
&#xD;
        2. Secondary - To determine the efficacy of TTAC-0001 in patients with recurrent&#xD;
           glioblastoma.&#xD;
&#xD;
        3. Exploratory&#xD;
&#xD;
             -  To evaluate pharmacokinetic (PK) parameters of TTAC-0001 in patients with recurrent&#xD;
                glioblastoma&#xD;
&#xD;
             -  To evaluate pharmacodynamic (PD) parameters by clinical biomarker test&#xD;
&#xD;
      Study Methodology&#xD;
&#xD;
      Patients will be sequentially enrolled from the 1st arm. An enrollment criterion to the next&#xD;
      arm is defined as no patients in the previous treatment arm showing grade ≥3 of hemangioma or&#xD;
      other Dose Limiting Toxicities (DLT). A safety review committee (SRC) will convene to&#xD;
      determine the patient's safety with a decision on enrollment into the next arm or change in&#xD;
      dosing frequency of study drug in the above case.&#xD;
&#xD;
      A patient who is withdrawn from the study before the completion of the 1st cycle can be&#xD;
      replaced with another patient. Patients will be treated for up to 1 year, unless a cause for&#xD;
      termination occurs, such as progression of disease (PD) or the withdrawal of consent.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 4, 2016</start_date>
  <completion_date type="Actual">June 2, 2017</completion_date>
  <primary_completion_date type="Actual">June 2, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to 1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS at 6-month time point</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>The rate of complete response and partial response assessed according to RANO criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate(DCR)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>The rate of complete response(CR), partial response(PR) and stable disease(SD) assessed according to RANO criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>up to 1 year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Area under the concentration-time curve (AUC)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Minimum plasma concentration (Cmin)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Volume of distribution (Vd)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Half-life (t1/2)</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacokinetics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Angiogenic factors in serum or changes in concentration</measure>
    <time_frame>up to 1 year</time_frame>
    <description>Pharmacodynamics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Perfusion parameter assessed by DCE-MRI</measure>
    <time_frame>every 2 cycles(each cycle is 4 weeks), up to 1year</time_frame>
    <description>Pharmacodynamics profile</description>
  </other_outcome>
  <other_outcome>
    <measure>Expression of angiogenic factors in endothelial cells</measure>
    <time_frame>At screening</time_frame>
    <description>Analyzed by IHC of tumor tissue</description>
  </other_outcome>
  <other_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Day 1 of every cycle(each cycle is 4 weeks), up to 1 year</time_frame>
    <description>Anti-drug (TTAC-0001) antibody (ADA) test for evaluation of immunogenicity</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Recurrent Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with 8mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with 12mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with 12mg/kg of TTAC-0001 weekly in every 4 weeks of cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TTAC-0001</intervention_name>
    <description>Calculated amount of drug will be diluted with normal saline and administered intravenously.</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <other_name>Tanibirumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Both male and female patients ≥19 years old&#xD;
&#xD;
          -  Diagnosed with primary glioblastoma by histopathological examination and confirmed&#xD;
             recurrent glioblastoma by magnetic resonance imaging (MRI) scans after concomitant&#xD;
             temozolomide chemotherapy with radiotherapy (CCRT). One previous&#xD;
             recurrence/progression of glioblastoma with reintroduction/altered schedule of&#xD;
             temozolomide is allowable.&#xD;
&#xD;
          -  At least one confirmed measurable lesion or non measurable lesion by response&#xD;
             assessment in neuro-oncology (RANO) criteria&#xD;
&#xD;
          -  Karnofsky Performance Status (KPS) ≥ 80&#xD;
&#xD;
          -  A person who satisfies the following criteria in hematologic, renal, and hepatic&#xD;
             function tests&#xD;
&#xD;
          -  At least 12 weeks of expected survival time&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with other malignant tumor within 2years&#xD;
&#xD;
          -  Uncontrolled HT or seizure, class III or IV heart failure, oxygen dependent disease,&#xD;
             active psychiatric disorder&#xD;
&#xD;
          -  Not recovered grade 2 AE due to previous CCRT&#xD;
&#xD;
          -  Major surgery or other investigational drug treatment within 4 weeks&#xD;
&#xD;
          -  Pregnant/lactating female and female/male potential childbearing without contraception&#xD;
&#xD;
          -  Severe drug hypersensitivity or hypersensitivity to a therapy similar to the study&#xD;
             drug&#xD;
&#xD;
          -  Expectation of poor compliance&#xD;
&#xD;
          -  Previous therapy with VEGF targeted agent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</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>Glioblastoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03033524
org study id: PMC_TTAC-0001_02
nct id: NCT03033524
lead sponsor: 
has dmc: Yes
Study Design - Multicenter, open-label, 3 arms, stepwise, phase Ⅱa clinical trial

      Study objective:

        1. Primary - To evaluate the safety of TTAC-0001 in patients with recurrent glioblastoma.

        2. Secondary - To determine the efficacy of TTAC-0001 in patients with recurrent
           glioblastoma.

        3. Exploratory

             -  To evaluate pharmacokinetic (PK) parameters of TTAC-0001 in patients with recurrent
                glioblastoma

             -  To evaluate pharmacodynamic (PD) parameters by clinical biomarker test

      Study Methodology

      Patients will be sequentially enrolled from the 1st arm. An enrollment criterion to the next
      arm is defined as no patients in the previous treatment arm showing grade ≥3 of hemangioma or
      other Dose Limiting Toxicities (DLT). A safety review committee (SRC) will convene to
      determine the patient's safety with a decision on enrollment into the next arm or change in
      dosing frequency of study drug in the above case.

      A patient who is withdrawn from the study before the completion of the 1st cycle can be
      replaced with another patient. Patients will be treated for up to 1 year, unless a cause for
      termination occurs, such as progression of disease (PD) or the withdrawal of consent.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events
time frame: up to 1 year
measure: PFS at 6-month time point
time frame: 6 months
measure: Objective response rate (ORR)
time frame: up to 1 year
description: The rate of complete response and partial response assessed according to RANO criteria.
measure: Disease control rate(DCR)
time frame: up to 1 year
description: The rate of complete response(CR), partial response(PR) and stable disease(SD) assessed according to RANO criteria.
measure: Overall survival(OS)
time frame: up to 1 year
measure: Area under the concentration-time curve (AUC)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Maximum plasma concentration (Cmax)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Minimum plasma concentration (Cmin)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Clearance (CL)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Volume of distribution (Vd)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Half-life (t1/2)
time frame: up to 1 year
description: Pharmacokinetics profile
measure: Angiogenic factors in serum or changes in concentration
time frame: up to 1 year
description: Pharmacodynamics profile
measure: Perfusion parameter assessed by DCE-MRI
time frame: every 2 cycles(each cycle is 4 weeks), up to 1year
description: Pharmacodynamics profile
measure: Expression of angiogenic factors in endothelial cells
time frame: At screening
description: Analyzed by IHC of tumor tissue
measure: Immunogenicity
time frame: Day 1 of every cycle(each cycle is 4 weeks), up to 1 year
description: Anti-drug (TTAC-0001) antibody (ADA) test for evaluation of immunogenicity
arm group label: Cohort 1
arm group type: Experimental
description: Patients will be treated with 8mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle.
arm group label: Cohort 2
arm group type: Experimental
description: Patients will be treated with 12mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle.
arm group label: Cohort 3
arm group type: Experimental
description: Patients will be treated with 12mg/kg of TTAC-0001 weekly in every 4 weeks of cycle.
intervention type: Drug
intervention name: TTAC-0001
description: Calculated amount of drug will be diluted with normal saline and administered intravenously.
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
other name: Tanibirumab
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Recurrence
sharing ipd: Undecided