<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/NCT03770624</url>
  </required_header>
  <id_info>
    <org_study_id>QL-007-003</org_study_id>
    <nct_id>NCT03770624</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety, Efficacy and PK of Multiple Doses of QL-007 in Chronic Hepatitis B Patients in CHINA</brief_title>
  <acronym>QL-007</acronym>
  <official_title>An Open-Label Phase 1b Study to Evaluate the Dose-Related Safety, Efficacy, and Pharmacokinetic Profile of Different Doses of QL-007 in Chronic Hepatitis B Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Qilu Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Qilu Pharmaceutical 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 is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60&#xD;
      patients with chronic HBV infection to determine the safety, preliminary efficacy, and&#xD;
      pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a&#xD;
      fasted state at the following planned dose levels: 200, 400, and then 600 mg.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60&#xD;
      patients with chronic HBV infection to determine the safety, preliminary efficacy, and&#xD;
      pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a&#xD;
      fasted state at the following planned dose levels: 200, 400, and then 600 mg.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Anticipated">April 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2019</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28</measure>
    <time_frame>Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28</time_frame>
    <description>Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax) of QL-007 following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time to Cmax (tmax) of QL-007 following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ of QL-007 following multiple doses following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal elimination half-life) of QL-007 following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses</measure>
    <time_frame>Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose</time_frame>
    <description>Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28</measure>
    <time_frame>Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28</time_frame>
    <description>Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events (AEs)</measure>
    <time_frame>From randomization up to Day 35</time_frame>
    <description>AEs occur during the study</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <arm_group>
    <arm_group_label>200 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet QL-007 will be administered orally daily (200 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>400 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet QL-007 will be administered orally daily (400 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>600 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet QL-007 will be administered orally daily (600 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet QL-007 will be administered orally daily (100 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet QL-007 will be administered orally daily (200 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TDF 300 mg QD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>TDF will be administered orally daily (300 mg QD) over the 28 days not request fast .</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QL-007 tablet</intervention_name>
    <description>QL-007 will be administered orally daily over the 28 days under fasted state.</description>
    <arm_group_label>100 mg BID</arm_group_label>
    <arm_group_label>200 mg BID</arm_group_label>
    <arm_group_label>200 mg QD</arm_group_label>
    <arm_group_label>400 mg QD</arm_group_label>
    <arm_group_label>600 mg QD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TDF</intervention_name>
    <description>TDF will be administered orally daily over the 28 days e.</description>
    <arm_group_label>TDF 300 mg QD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic Hepatitis B infection, defined as positive test for Hepatitis B surface&#xD;
             antigen (HBsAg) for more than 6 months prior to randomization&#xD;
&#xD;
          -  HBV DNA at screening greater than or equal to (&gt;/=) 2 × 10^4 international units per&#xD;
             milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or &gt;/=2 ×&#xD;
             10^3 IU/mL for HBeAg-negative participants&#xD;
&#xD;
          -  ALT&gt; 1 x upper limit of normal (ULN) and &lt; 10 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside&#xD;
             therapy with the last dose ≥4 weeks prior to screening are also eligible.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)&#xD;
&#xD;
          -  Presence of autoimmune disorders&#xD;
&#xD;
          -  History of liver disease other than Hepatitis B&#xD;
&#xD;
          -  History of Gilbert's Disease&#xD;
&#xD;
          -  Any sign of decompensated liver disease&#xD;
&#xD;
          -  Known or suspected cirrhosis&#xD;
&#xD;
          -  Evidence of hepatocellular carcinoma&#xD;
&#xD;
          -  Patient has clinically significant, uncontrolled heart disease and/or recent cardiac&#xD;
             event (within 6 months)&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Alcohol or substance abuse&#xD;
&#xD;
          -  History of bleeding diathesis&#xD;
&#xD;
          -  Patients with a history of seizures, central nervous system disorders or psychiatric&#xD;
             disability thought to be clinically significant in the opinion of the investigator.&#xD;
&#xD;
          -  History of clinically significant gastrointestinal, cardiovascular, endocrine, renal,&#xD;
             ocular, pulmonary, psychiatric or neurological disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Peking</city>
        <state>Beijing</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guiqiang Wang, Dr</last_name>
      <phone>13911405123</phone>
      <email>John131212@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>June 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>December 7, 2018</last_update_submitted>
  <last_update_submitted_qc>December 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2018</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>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03770624
org study id: QL-007-003
nct id: NCT03770624
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60
      patients with chronic HBV infection to determine the safety, preliminary efficacy, and
      pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a
      fasted state at the following planned dose levels: 200, 400, and then 600 mg.
This is a randomized, open-label, positive-control, dose-escalation Phase 1b trial in 60
      patients with chronic HBV infection to determine the safety, preliminary efficacy, and
      pharmacokinetics (PK) of QL-007 after administration over 28 days of multiple oral doses in a
      fasted state at the following planned dose levels: 200, 400, and then 600 mg.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in serum HBV DNA from baseline at Day3, 8, 15, 22 and 28
time frame: Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
description: Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days
measure: Peak Plasma Concentration (Cmax) of QL-007 following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: The time to Cmax (tmax) of QL-007 following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: AUC0-t (area under the plasma concentration versus time curve) of QL-007 following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: AUC0-∞ of QL-007 following multiple doses following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: t1/2 (terminal elimination half-life) of QL-007 following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: Vz/F(apparent volume of distribution for the terminal disposition phase) of QL-007 following multiple doses
time frame: Days 1, 3, 8, 15, 22, and 28. On Days 1, 3, 8, 15, 22, and 28, samples will be collected predose; on Days 1 and 28, samples will also be collected at 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h postdose
description: Concentrations of QL-007 in plasma will be collected on Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28.
measure: Change in serum HBsAg from baseline at Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
time frame: Time Frame: Day 1, Day 3, Day 8, Day 15, Day 22 and Day 28
description: Blood samples will be collected on Day -1 , 1, 3, 8, 15, 22, 28 and the follow-up 7 ±1 days
measure: adverse events (AEs)
time frame: From randomization up to Day 35
description: AEs occur during the study
arm group label: 200 mg QD
arm group type: Experimental
description: Tablet QL-007 will be administered orally daily (200 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.
arm group label: 400 mg QD
arm group type: Experimental
description: Tablet QL-007 will be administered orally daily (400 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.
arm group label: 600 mg QD
arm group type: Experimental
description: Tablet QL-007 will be administered orally daily (600 mg QD) over the 28 days under fasted state. Patients fast for 10h before administration and 1h after administration.
arm group label: 100 mg BID
arm group type: Experimental
description: Tablet QL-007 will be administered orally daily (100 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.
arm group label: 200 mg BID
arm group type: Experimental
description: Tablet QL-007 will be administered orally daily (200 mg BID) over the 28 days under fasted state. Patients fast for 2h before administration and 1h after administration.
arm group label: TDF 300 mg QD
arm group type: Active Comparator
description: TDF will be administered orally daily (300 mg QD) over the 28 days not request fast .
intervention type: Drug
intervention name: QL-007 tablet
description: QL-007 will be administered orally daily over the 28 days under fasted state.
arm group label: 100 mg BID
arm group label: 200 mg BID
arm group label: 200 mg QD
arm group label: 400 mg QD
arm group label: 600 mg QD
intervention type: Drug
intervention name: TDF
description: TDF will be administered orally daily over the 28 days e.
arm group label: TDF 300 mg QD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
sharing ipd: No