<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/NCT03815812</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI306B101</org_study_id>
    <nct_id>NCT03815812</nct_id>
  </id_info>
  <brief_title>Multiple Ascending Dose Study of PCSK-9 Inhibitor (IBI306) in Chinese Patients With Hypercholesterolemia</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Repeated-dosing, Multiple Ascending Dose Trial to Evaluate the Safety and Tolerability of a Novel PCSK-9 Anti-body, IBI306, in Chinese Patients With Hypercholesterolemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Innovent Biologics (Suzhou) Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Innovent Biologics (Suzhou) Co. Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      IBI306 is a fully human monoclonal antibody that binds proprotein convertase&#xD;
      substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density&#xD;
      lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and&#xD;
      low-density lipoprotein cholesterol（LDL-C）uptake. In phase I study IBI306 was shown to be&#xD;
      safe and well tolerated. There was robust reduction in LDL-C, Apo(B), non-HDL-C and&#xD;
      lipoprotein (a) in healthy subjects. This study is a randomized, double-blind,&#xD;
      placebo-controlled, repeated-dosing, multiple ascending dose trial to evaluate the safety and&#xD;
      tolerability of a novel PCSK-9 anti-body, IBI306, in Chinese patients with&#xD;
      hypercholesterolemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 60 patients who meet the criteria for admission and have a clinical diagnosis of&#xD;
      hypercholesterolemia and have received statin for at least 4 weeks will be randomized and&#xD;
      receive different dose groups of IBI306 or matching placebo. Ascending dose design includes 6&#xD;
      dose levels: 75 mg Q2W, 140 mgQ2W, 300 mg Q4W，420mg Q4W, 450 mg Q6W，and 600 mg Q6W. Total&#xD;
      duration of the study per subject is 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 7, 2019</start_date>
  <completion_date type="Anticipated">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">July 12, 2019</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AEs/SAEs</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>• Percentage of participants with adverse events and severity of adverse events from the first dose to the last visit</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>area under curve (AUC)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>volume of distribution (Vd)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>half-life (T1/2)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clearance (CL)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>accumulation factor (AR)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in blood PCSK-9 concentrations at different time points before and after administration relative to baseline</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADA</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>The occurrence of anti-IBI306 antibody (ADA) in serum before and after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAb</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>The occurrence of neutralizing antibody (NAb) in serum before and after administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in LDL-C from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in LDL-C levels from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in non-HDL-C cholesterol levels from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in ApoB from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in ApoB/ApoA1 ratio from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of patients with a 15% or more decrease in LDL-C levels from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in Lp(a) from baseline at 12 weeks</measure>
    <time_frame>baseline and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in mean LDL-C levels at week 6 and 12 relative to baseline</measure>
    <time_frame>baseline, week 6 and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in mean ApoB levels at week 6 and 12 relative to baseline</measure>
    <time_frame>baseline, week 6 and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in mean Lp(a) levels at week 6 and 12 relative to baseline</measure>
    <time_frame>baseline, week 6 and 12</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>IBI306</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received one of 6 dose levels of IBI306 administered as multiple subcutaneous dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received matching placebo dose regimen by subcutaneous injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI306</intervention_name>
    <description>Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W</description>
    <arm_group_label>IBI306</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must meet all of the following inclusion criteria in order to be included in&#xD;
             the study:&#xD;
&#xD;
               -  Provide a signed and dated informed consent form;&#xD;
&#xD;
               -  Men or women with an age of 18 to 70 years of age at screening (Inclusive);&#xD;
&#xD;
               -  BMI between18kg/m2 and 30kg/m2(Inclusive);&#xD;
&#xD;
               -  Diagnosis of hyperlipidemia, and taking statins with moderate doses or above for&#xD;
                  at least 4 weeks;&#xD;
&#xD;
               -  Fasting LDL-C between 100 mg / dl (2.6 mmol / L) and 220 mg / dl (5.7 mmol / L)&#xD;
                  at screening (Inclusive);&#xD;
&#xD;
               -  Fasting triglycerides ≤ 400 mg (4.5 mmol / L) at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who do not meet any of the following exclusion criteria cannot be included in&#xD;
             the study:&#xD;
&#xD;
               -  Subject's current statin treatment are stable less than 4 weeks prior to random&#xD;
                  enrollment&#xD;
&#xD;
               -  New York Heart Association (NYHA) III or IV heart failure, or last left&#xD;
                  ventricular ejection fraction &lt;30%&#xD;
&#xD;
               -  Uncontrolled hypertension, defined as repeated measurements confirmed, sitting&#xD;
                  systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.&#xD;
&#xD;
               -  Diabetic patients have one of the following conditions;&#xD;
&#xD;
                    1. Known microvascular and macrovascular complications&#xD;
&#xD;
                    2. HbA1c&gt;7.5% within 4 weeks before screening&#xD;
&#xD;
               -  Moderate or severe renal insufficiency, defined as the estimated glomerular&#xD;
                  filtration rate &lt;60 ml / min / 1.73 m2 during screening (calculated using the&#xD;
                  MDRD formula)&#xD;
&#xD;
               -  Active liver disease or impaired liver function, defined as aspartate&#xD;
                  aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 3 times the normal&#xD;
                  upper limit (ULN) at screening.&#xD;
&#xD;
               -  Have previously undergone liver transplant surgery.&#xD;
&#xD;
               -  Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) at screening.&#xD;
&#xD;
               -  At the discretion of the investigator, there are known active infections or major&#xD;
                  blood, kidney, metabolism, gastrointestinal or endocrine dysfunction.&#xD;
&#xD;
               -  Female subject of childbearing potential not willing to use an acceptable&#xD;
                  method(s) of effective birth control during treatment with investigational&#xD;
                  product and for an additional 15 weeks after the end of treatment with&#xD;
                  investigational product. Male subjects are reluctant to inform their female&#xD;
                  sexual partners about their participation in the clinical study.&#xD;
&#xD;
               -  Female subject is pregnant or breast feeding, planning to become pregnant or&#xD;
                  planning to breastfeed during treatment with investigational product and/or&#xD;
                  within 15 weeks after the end of treatment with investigational product..&#xD;
&#xD;
               -  Subjects have been treated with PCSK9 inhibitors or have participated in other&#xD;
                  PCSK-9 inhibitor studies&#xD;
&#xD;
               -  Subject has known sensitivity to the study drug and its excipients&#xD;
&#xD;
               -  Any conditions which, in the opinion of the Investigator, would make the subject&#xD;
                  unsuitable for enrollment (for example, alcohol or other substance abuse, unable&#xD;
                  or unwilling to comply with the agreement or mental illness).&#xD;
&#xD;
               -  Currently receiving treatment in another investigational device or drug study, or&#xD;
                  less than 30 days before randomization since ending treatment on another&#xD;
                  investigational device or drug study(s) while participating in this study&#xD;
&#xD;
               -  In the opinion of the investigator, would pose a risk to subject safety or&#xD;
                  interfere with the study evaluation, procedures or completion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>September 2, 2019</last_update_submitted>
  <last_update_submitted_qc>September 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2019</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>Hypercholesterolemia</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/NCT03815812
org study id: CIBI306B101
nct id: NCT03815812
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
IBI306 is a fully human monoclonal antibody that binds proprotein convertase
      substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density
      lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and
      low-density lipoprotein cholesterol（LDL-C）uptake. In phase I study IBI306 was shown to be
      safe and well tolerated. There was robust reduction in LDL-C, Apo(B), non-HDL-C and
      lipoprotein (a) in healthy subjects. This study is a randomized, double-blind,
      placebo-controlled, repeated-dosing, multiple ascending dose trial to evaluate the safety and
      tolerability of a novel PCSK-9 anti-body, IBI306, in Chinese patients with
      hypercholesterolemia.
A total of 60 patients who meet the criteria for admission and have a clinical diagnosis of
      hypercholesterolemia and have received statin for at least 4 weeks will be randomized and
      receive different dose groups of IBI306 or matching placebo. Ascending dose design includes 6
      dose levels: 75 mg Q2W, 140 mgQ2W, 300 mg Q4W，420mg Q4W, 450 mg Q6W，and 600 mg Q6W. Total
      duration of the study per subject is 12 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: AEs/SAEs
time frame: up to 12 weeks
description: • Percentage of participants with adverse events and severity of adverse events from the first dose to the last visit
measure: Tmax
time frame: up to 12 weeks
measure: Cmax
time frame: up to 12 weeks
measure: area under curve (AUC)
time frame: up to 12 weeks
measure: volume of distribution (Vd)
time frame: up to 12 weeks
measure: half-life (T1/2)
time frame: up to 12 weeks
measure: clearance (CL)
time frame: up to 12 weeks
measure: accumulation factor (AR)
time frame: up to 12 weeks
measure: changes in blood PCSK-9 concentrations at different time points before and after administration relative to baseline
time frame: up to 12 weeks
measure: ADA
time frame: up to 12 weeks
description: The occurrence of anti-IBI306 antibody (ADA) in serum before and after administration
measure: NAb
time frame: up to 12 weeks
description: The occurrence of neutralizing antibody (NAb) in serum before and after administration
measure: Percent change in LDL-C from baseline at 12 weeks
time frame: baseline and week 12
measure: Changes in LDL-C levels from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent change in non-HDL-C cholesterol levels from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent change in ApoB from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent change in ApoB/ApoA1 ratio from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent of patients with a 15% or more decrease in LDL-C levels from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent change in Lp(a) from baseline at 12 weeks
time frame: baseline and week 12
measure: Percent change in mean LDL-C levels at week 6 and 12 relative to baseline
time frame: baseline, week 6 and 12
measure: Percent change in mean ApoB levels at week 6 and 12 relative to baseline
time frame: baseline, week 6 and 12
measure: Percent change in mean Lp(a) levels at week 6 and 12 relative to baseline
time frame: baseline, week 6 and 12
arm group label: IBI306
arm group type: Experimental
description: Participants received one of 6 dose levels of IBI306 administered as multiple subcutaneous dose
arm group label: placebo
arm group type: Placebo Comparator
description: Participants received matching placebo dose regimen by subcutaneous injection.
intervention type: Drug
intervention name: IBI306
description: Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W
arm group label: IBI306
intervention type: Drug
intervention name: placebo
description: Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Hypercholesterolemia
sharing ipd: No