<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/NCT04466137</url>
  </required_header>
  <id_info>
    <org_study_id>TB1801CSF</org_study_id>
    <nct_id>NCT04466137</nct_id>
  </id_info>
  <brief_title>Phase 3 Study to Evaluate the Safety and Efficacy of YPEG-rhG-CSF in Malignancies Receiving Chemotherapy</brief_title>
  <official_title>A Multi-centers, Randomized, Open-labeled, Positive-controlled, Phase 3 Study to Evaluate the Safety and Efficacy of YPEG-rhG-CSF, Once-per-cycle, in Patients With Malignancies Receiving Myelosuppressive Chemotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xiamen Amoytop Biotech Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Xiamen Amoytop Biotech Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase 3 study is aimed to evaluate the safety and efficacy of YPEG-rhG-CSF in reducing&#xD;
      the infection manifested by febrile neutropenia in patients with non-myeloid malignancy who&#xD;
      receiving Myelosuppressive Chemotherapy which is likely to cause clinically significant&#xD;
      febrile neutropenia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2020</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 24, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Duration of Severe Neutropenia (DSN) During Cycle 1.</measure>
    <time_frame>At the end of Cycle 1 (21 days one cycle)</time_frame>
    <description>Mean duration of severe neutropenia, defined as number of consecutive days with absolute neutrophil count (ANC) &lt;0.5 × 10^9 cells/l (grade 4 neutropenia)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Febrile neutropenia(FN).</measure>
    <time_frame>Cycle1 to Cycle 4(21 days one cycle)</time_frame>
    <description>FN defines as the ANC counts is less than &lt; 0.5 × 10^9 cells/L or ANC counts between 0.5 × 10^9 cells/L and 1.0 × 10^9 cells/L but probably to decline to less than 0.5×10^9 cells/L within 48hrs, and body temperature is higher than 38.3 degrees Celsius or higher than 38.0 degrees Celsius and lasting for more than 1hr.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean duration of DSN.</measure>
    <time_frame>Cycle2 to Cycle 4 (21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Grade 3 neutropenia.</measure>
    <time_frame>Cycle1 to Cycle 4 ( 21 days one cycle)</time_frame>
    <description>Grade 3 neutropenia defines as the ANC count is less than 1.0×10^9 cells/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean duration of grade 3 neutropenia.</measure>
    <time_frame>Cycle1 to Cycle 4(21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutrophils dynamic changes from baseline.</measure>
    <time_frame>Cycle1 to Cycle 4 ( 21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of neutrophils recovering to over 2.0×10^9 cells/L after nadir.</measure>
    <time_frame>Cycle1 to Cycle 4 (21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with antibiotic usage.</measure>
    <time_frame>Cycle1 to Cycle 4 ( 21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients experienced infection.</measure>
    <time_frame>Cycle1 to Cycle 4 ( 21 days one cycle)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients fulfilling expected chemotherapy.</measure>
    <time_frame>Cycle1 to Cycle 4 (21 days one cycle)</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">398</enrollment>
  <condition>Non-Myeloid Malignancy</condition>
  <arm_group>
    <arm_group_label>YPEG-rhG-CSF 2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YPEG-rhG-CSF 2mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>YPEG-rhG-CSF 33μg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YPEG-rhG-CSF 33μg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Positive Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>rhG-CSF/PEG-rhG-CSF</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YPEG-rhG-CSF</intervention_name>
    <description>YPEG-rhG-CSF 2mg, single s.c. at day 3 of each cycles, up to 4 cycles. 21 day one cycles.</description>
    <arm_group_label>YPEG-rhG-CSF 2mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YPEG-rhG-CSF</intervention_name>
    <description>YPEG-rhG-CSF 33μg/kg, single s.c. at day 3 of each cycles, up to 4 cycles. 21 day one cycles.</description>
    <arm_group_label>YPEG-rhG-CSF 33μg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhG-CSF/PEG-rhG-CSF</intervention_name>
    <description>rhG-CSF 5μg/kg/day, s.c. from day 3 to day 14 or until neutrophils recover to exceed 5.0×10^9 cells/L, whichever comes first, in the first cycle. Patient can still continue rhG-CSF 5μg/kg/day, or covert to PEG-rhG-CSF 6mg/Cycle in the following 2-4 cycle. 21 day one cycles.</description>
    <arm_group_label>Positive Control Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathology and/or cytology diagnosed as breast cancer (BC) or non-small cell lung&#xD;
             cancer (NSCLC), and patients with breast cancer is suitable to receive&#xD;
             TAC(Docetaxel,Doxorubicin combined with Cyclophosphamide) chemotherapy, while patients&#xD;
             with NSCLC is suitable to receive DC(Docetaxel combined with Carboplatin)&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Age ≥18 yrs.&#xD;
&#xD;
          -  Weight ≥45 kg.&#xD;
&#xD;
          -  Karnofsky Score ≥ 70.&#xD;
&#xD;
          -  Life Expectancy ≥ 3 months.&#xD;
&#xD;
          -  Peripheral blood test: WBC≥3.5×10^9 cells/L, PLT≥100×10^9 cells/L. ANC≥1.5×10^9&#xD;
             cells/L.&#xD;
&#xD;
          -  Understand and voluntarily sign the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving chemotherapy within two months prior to screening.&#xD;
&#xD;
          -  Previously or plan to receive radiotherapy (&gt;25% total bone marrow volume).&#xD;
&#xD;
          -  Evidence of tumor metastasis in bone marrow.&#xD;
&#xD;
          -  Lack of awareness.&#xD;
&#xD;
          -  Uncontrolled infection or using of antibiotics within 72hrs prior to screening.&#xD;
&#xD;
          -  Previously received or plan to undergoing bone marrow or organ transplants.&#xD;
&#xD;
          -  Patients with bleeding tendency, e.g. prolonged prothrombin time of more than 3&#xD;
             seconds.&#xD;
&#xD;
          -  Dysfunction in heart,lung, liver, kidney, or other major organs or systems; ALT&gt;2.5&#xD;
             ULN (upper limit of normal), TBil &gt;2.5 ULN (ALT&gt;2.5 ULN, total bilirubin &gt;2.5 ULN for&#xD;
             patients with liver metastasis), HBsAg positive, anti-HCV positive, evidence of liver&#xD;
             decompensation, or Cr &gt;1.5 ULN.&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Malignancy other than BC or NSCLC.&#xD;
&#xD;
          -  Hypersensitivity to rhG-CSF or any component of the investigational Products.&#xD;
&#xD;
          -  Subject enrolled in any other studies within 3 months prior to screening.&#xD;
&#xD;
          -  Drug abuser or alcoholics.&#xD;
&#xD;
          -  Any other conditions which in the opinion of the investigator precluded enrollment&#xD;
             into the study.&#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>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>February 7, 2022</last_update_submitted>
  <last_update_submitted_qc>February 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>G-CSF</keyword>
  <keyword>Human Granulocyte Colony-Stimulating Factor</keyword>
  <keyword>Febrile Neutropenia</keyword>
  <keyword>Neutropenia</keyword>
  <keyword>Myelosuppressive Chemotherapy</keyword>
  <keyword>FN</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04466137
org study id: TB1801CSF
nct id: NCT04466137
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This phase 3 study is aimed to evaluate the safety and efficacy of YPEG-rhG-CSF in reducing
      the infection manifested by febrile neutropenia in patients with non-myeloid malignancy who
      receiving Myelosuppressive Chemotherapy which is likely to cause clinically significant
      febrile neutropenia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean Duration of Severe Neutropenia (DSN) During Cycle 1.
time frame: At the end of Cycle 1 (21 days one cycle)
description: Mean duration of severe neutropenia, defined as number of consecutive days with absolute neutrophil count (ANC) <0.5 × 10^9 cells/l (grade 4 neutropenia)
measure: Incidence of Febrile neutropenia(FN).
time frame: Cycle1 to Cycle 4(21 days one cycle)
description: FN defines as the ANC counts is less than < 0.5 × 10^9 cells/L or ANC counts between 0.5 × 10^9 cells/L and 1.0 × 10^9 cells/L but probably to decline to less than 0.5×10^9 cells/L within 48hrs, and body temperature is higher than 38.3 degrees Celsius or higher than 38.0 degrees Celsius and lasting for more than 1hr.
measure: Mean duration of DSN.
time frame: Cycle2 to Cycle 4 (21 days one cycle)
measure: Incidence of Grade 3 neutropenia.
time frame: Cycle1 to Cycle 4 ( 21 days one cycle)
description: Grade 3 neutropenia defines as the ANC count is less than 1.0×10^9 cells/L.
measure: Mean duration of grade 3 neutropenia.
time frame: Cycle1 to Cycle 4(21 days one cycle)
measure: Neutrophils dynamic changes from baseline.
time frame: Cycle1 to Cycle 4 ( 21 days one cycle)
measure: Time of neutrophils recovering to over 2.0×10^9 cells/L after nadir.
time frame: Cycle1 to Cycle 4 (21 days one cycle)
measure: Proportion of patients with antibiotic usage.
time frame: Cycle1 to Cycle 4 ( 21 days one cycle)
measure: Proportion of patients experienced infection.
time frame: Cycle1 to Cycle 4 ( 21 days one cycle)
measure: Proportion of patients fulfilling expected chemotherapy.
time frame: Cycle1 to Cycle 4 (21 days one cycle)
arm group label: YPEG-rhG-CSF 2mg
arm group type: Experimental
description: YPEG-rhG-CSF 2mg
arm group label: YPEG-rhG-CSF 33μg/kg
arm group type: Experimental
description: YPEG-rhG-CSF 33μg/kg
arm group label: Positive Control Group
arm group type: Active Comparator
description: rhG-CSF/PEG-rhG-CSF
intervention type: Drug
intervention name: YPEG-rhG-CSF
description: YPEG-rhG-CSF 2mg, single s.c. at day 3 of each cycles, up to 4 cycles. 21 day one cycles.
arm group label: YPEG-rhG-CSF 2mg
intervention type: Drug
intervention name: YPEG-rhG-CSF
description: YPEG-rhG-CSF 33μg/kg, single s.c. at day 3 of each cycles, up to 4 cycles. 21 day one cycles.
arm group label: YPEG-rhG-CSF 33μg/kg
intervention type: Drug
intervention name: rhG-CSF/PEG-rhG-CSF
description: rhG-CSF 5μg/kg/day, s.c. from day 3 to day 14 or until neutrophils recover to exceed 5.0×10^9 cells/L, whichever comes first, in the first cycle. Patient can still continue rhG-CSF 5μg/kg/day, or covert to PEG-rhG-CSF 6mg/Cycle in the following 2-4 cycle. 21 day one cycles.
arm group label: Positive Control Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms