<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/NCT01663441</url>
  </required_header>
  <id_info>
    <org_study_id>NL201-Ⅲ-2012</org_study_id>
    <nct_id>NCT01663441</nct_id>
  </id_info>
  <brief_title>A Phase Ⅲa Study of Genetically Modified Recombinant Human Interleukin-11</brief_title>
  <official_title>Multicenter, Randomized Phase Ⅲa Study of Genetically Modified Recombinant Human Interleukin-11 to Prevent Chemotherapy-induced Thrombocytopenia in Cancer Patients Receiving Chemotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Northland Biotech. Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Northland Biotech. Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phases Ⅲ trials is divided into two stages,Ⅲa and Ⅲb.The aim of Ⅲa is to evaluate the&#xD;
      optimal dosing dose of genetically modified recombinant human IL-11 (mIL-11) in a multicenter&#xD;
      randomized self-control trial involving 60 cancer patients undergoing chemotherapy.The aim of&#xD;
      Ⅲb is to evaluate the efficacy and safety of genetically modified recombinant human IL-11&#xD;
      (mIL-11), using rhIL-11 as an active control, in a multicenter randomized trial involving 240&#xD;
      cancer patients undergoing chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators recently developed a mutant form of rhIL-11 with improved stability. In in&#xD;
      vitro experimental systems, mIL-11 was shown to endure chemical and proteolytic stresses more&#xD;
      effectively, while retaining the biological activity of the original rhIL-11. The improved&#xD;
      stability of mIL-11 was also demonstrated in the comparative pharmacokinetic study of&#xD;
      subcutaneously delivered mIL-11 and rhIL-11 in the rodent and primate models. Based on its&#xD;
      improved pharmacokinetic and pharmacodynamic features. In Phase II study shows that mIL-11 is&#xD;
      well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose&#xD;
      of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT. This study is&#xD;
      a phase III, single-blinded, randomized,multicenter,cross-over study designed to evaluate&#xD;
      optimal dosing dose and efficacy and safety of mIL-11 on CIT patients receiving suitable&#xD;
      chemotherapeutic regimen for treating cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">August 2017</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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recovery time of platelet counts from below 100x10^9/L raise to more than 100 x10^9/L.</measure>
    <time_frame>During 21 days of chemotherapy cycles</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nadir platelet counts</measure>
    <time_frame>During 21 days of chemotherapy cycles</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet counts at day 21 after the initiation of chemotherapy.</measure>
    <time_frame>Day 21 after the initiation of chemotherapy.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average platelet counts</measure>
    <time_frame>During 21 days of chemotherapy cycles</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of thrombocytopenia</measure>
    <time_frame>During 21 days of chemotherapy cycles</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Chemotherapy-induced Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this treatment group will receive NL201(5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(7.5μg/kg).&#xD;
Only for Dose-finding in Phase Ⅲa.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this treatment group will receive NL201(7.5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(5μg/kg).&#xD;
Only for Dose-finding in Phase Ⅲa.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in this treatment group will receive NL201（optimal dosing dose）in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive rhIL-11(25μg/kg).&#xD;
Only in Phase Ⅲb.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in this treatment group will receive rhIL-11(25μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201（optimal dosing dose）.&#xD;
Only in Phase Ⅲb.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NL201</intervention_name>
    <description>mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；</description>
    <arm_group_label>A1</arm_group_label>
    <arm_group_label>A2</arm_group_label>
    <other_name>mIL-11</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NL201</intervention_name>
    <description>mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；</description>
    <arm_group_label>A1</arm_group_label>
    <arm_group_label>A2</arm_group_label>
    <other_name>mIL-11</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NL201</intervention_name>
    <description>The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <other_name>mIL-11</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhIL-11</intervention_name>
    <description>rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <other_name>Recombinant Human Interleukin-11 for Injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histological verification of malignancy at the time of initial diagnosis；&#xD;
&#xD;
          -  Patients (age,18-75 years) receiving chemotherapy, who had experienced platelet counts&#xD;
             below 75×10^9/L；&#xD;
&#xD;
          -  patients were required to have adequate bone marrow,hepatic, and renal functions at&#xD;
             the time of study entry；&#xD;
&#xD;
          -  ECOG ≤2；&#xD;
&#xD;
          -  patients to have normal laboratory findings:while white blood count&#xD;
             &gt;3.0×10^9/L,platelet count ≥100×10^9/L, and AST and/or ALT lesser than 2.5 times the&#xD;
             upper limit of the normal value；&#xD;
&#xD;
          -  The estimated life expectancy of the patient was more than 3 months.&#xD;
&#xD;
        Exclusion Criteria:；&#xD;
&#xD;
          -  patients who received total body irradiation；&#xD;
&#xD;
          -  patients with childbearing potential；&#xD;
&#xD;
          -  patients who were breast-feeding or pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Third Affiliated Hospital of Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Cancer Institute and Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.northland-bio.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chemotherapy</keyword>
  <keyword>Thrombocytopenia</keyword>
  <keyword>Interleukin-11</keyword>
  <keyword>Platelet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oprelvekin</mesh_term>
  </intervention_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/NCT01663441
org study id: NL201-Ⅲ-2012
nct id: NCT01663441
lead sponsor: 
has dmc: Yes
This phases Ⅲ trials is divided into two stages,Ⅲa and Ⅲb.The aim of Ⅲa is to evaluate the
      optimal dosing dose of genetically modified recombinant human IL-11 (mIL-11) in a multicenter
      randomized self-control trial involving 60 cancer patients undergoing chemotherapy.The aim of
      Ⅲb is to evaluate the efficacy and safety of genetically modified recombinant human IL-11
      (mIL-11), using rhIL-11 as an active control, in a multicenter randomized trial involving 240
      cancer patients undergoing chemotherapy.
The investigators recently developed a mutant form of rhIL-11 with improved stability. In in
      vitro experimental systems, mIL-11 was shown to endure chemical and proteolytic stresses more
      effectively, while retaining the biological activity of the original rhIL-11. The improved
      stability of mIL-11 was also demonstrated in the comparative pharmacokinetic study of
      subcutaneously delivered mIL-11 and rhIL-11 in the rodent and primate models. Based on its
      improved pharmacokinetic and pharmacodynamic features. In Phase II study shows that mIL-11 is
      well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose
      of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT. This study is
      a phase III, single-blinded, randomized,multicenter,cross-over study designed to evaluate
      optimal dosing dose and efficacy and safety of mIL-11 on CIT patients receiving suitable
      chemotherapeutic regimen for treating cancer.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Recovery time of platelet counts from below 100x10^9/L raise to more than 100 x10^9/L.
time frame: During 21 days of chemotherapy cycles
measure: Nadir platelet counts
time frame: During 21 days of chemotherapy cycles
measure: Platelet counts at day 21 after the initiation of chemotherapy.
time frame: Day 21 after the initiation of chemotherapy.
measure: Average platelet counts
time frame: During 21 days of chemotherapy cycles
measure: Incidence of thrombocytopenia
time frame: During 21 days of chemotherapy cycles
arm group label: A1
arm group type: Experimental
description: Patients in this treatment group will receive NL201(5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(7.5μg/kg).
Only for Dose-finding in Phase Ⅲa.
arm group label: A2
arm group type: Experimental
description: Patients in this treatment group will receive NL201(7.5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(5μg/kg).
Only for Dose-finding in Phase Ⅲa.
arm group label: A
arm group type: Active Comparator
description: Patients in this treatment group will receive NL201（optimal dosing dose）in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive rhIL-11(25μg/kg).
Only in Phase Ⅲb.
arm group label: B
arm group type: Active Comparator
description: Patients in this treatment group will receive rhIL-11(25μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201（optimal dosing dose）.
Only in Phase Ⅲb.
intervention type: Drug
intervention name: NL201
description: mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；
arm group label: A1
arm group label: A2
other name: mIL-11
intervention type: Drug
intervention name: NL201
description: mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；
arm group label: A1
arm group label: A2
other name: mIL-11
intervention type: Drug
intervention name: NL201
description: The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.
arm group label: A
arm group label: B
other name: mIL-11
intervention type: Drug
intervention name: rhIL-11
description: rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.
arm group label: A
arm group label: B
other name: Recombinant Human Interleukin-11 for Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
url: http://www.northland-bio.com/
description: Related Info
responsible party type: Sponsor
mesh term: Thrombocytopenia
mesh term: Oprelvekin