<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/NCT03263507</url>
  </required_header>
  <id_info>
    <org_study_id>ISIS 721744-CS1</org_study_id>
    <nct_id>NCT03263507</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Donidalorsen (IONIS-PKK-LRx) Administered Subcutaneously to Healthy Volunteers</brief_title>
  <official_title>A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 721744, an Antisense Oligonucleotide Inhibitor of PKK, Administered Subcutaneously to Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ionis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ionis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of&#xD;
      Donidalorsen administered subcutaneously to Healthy Volunteers&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">October 9, 2018</completion_date>
  <primary_completion_date type="Actual">October 9, 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of adverse events that are related to treatment with Donidalorsen</measure>
    <time_frame>Up to 176 days</time_frame>
    <description>The safety and tolerability of multiple doses of Donidalorsen will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with Donidalorsen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak plasma Concentration (Cmax) of Donidalorsen</measure>
    <time_frame>Up to 176 days</time_frame>
    <description>Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to peak plasma Concentration (Tmax) of Donidalorsen</measure>
    <time_frame>Up to 176 days</time_frame>
    <description>Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of Donidalorsen on plasma PKK concentration</measure>
    <time_frame>Up to 176 days</time_frame>
    <description>Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Donidalorsen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ascending single and multiple doses of Donidalorsen administered subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (sterile saline 0.9%)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Calculated volume to match active comparator</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Saline .9%</description>
    <arm_group_label>Placebo (sterile saline 0.9%)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donidalorsen</intervention_name>
    <description>Donidalorsen administered subcutaneously</description>
    <arm_group_label>Donidalorsen</arm_group_label>
    <other_name>ISIS 721744</other_name>
    <other_name>IONIS-PKK-LRx</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have given written informed consent and be able to comply with all study&#xD;
             requirements&#xD;
&#xD;
          -  Healthy males or females aged 18-65 inclusive at the time of Informed Consent&#xD;
&#xD;
          -  Females must be non-pregnant and non-lactating, and either surgically sterile or post-&#xD;
             menopausal&#xD;
&#xD;
          -  Males must be surgically sterile, abstinent or using an acceptable contraceptive&#xD;
             method&#xD;
&#xD;
          -  BMI &lt;35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically-significant abnormalities in medical history including acute coronary&#xD;
             syndrome, major surgery within 3 months of Screening, planned surgery that would occur&#xD;
             during the study or physical examination or other screening results such as ECGs at&#xD;
             Screening&#xD;
&#xD;
          -  Clinically significant hematologic, chemistry, and urine abnormalities&#xD;
&#xD;
          -  Treatment with another Study Drug, biological agent, or device within 4 weeks of&#xD;
             Screening&#xD;
&#xD;
          -  History of bleeding diathesis or coagulopathy&#xD;
&#xD;
          -  Smoking &gt;10 cigarettes per day&#xD;
&#xD;
          -  Considered unsuitable for inclusion by the Principal Investigator&#xD;
&#xD;
          -  Current use of concomitant medications (including herbal or OTC medications) unless&#xD;
             approved by Sponsor Medical Monitor&#xD;
&#xD;
          -  Known history or positive test for HIV, hepatitis C or chronic hepatitis B&#xD;
&#xD;
          -  Blood donation within 30 days of screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ionis Investigative Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M9L 3A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IONIS PKK-LRx</keyword>
  <!-- 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/NCT03263507
org study id: ISIS 721744-CS1
nct id: NCT03263507
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose is to assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of
      Donidalorsen administered subcutaneously to Healthy Volunteers
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence and severity of adverse events that are related to treatment with Donidalorsen
time frame: Up to 176 days
description: The safety and tolerability of multiple doses of Donidalorsen will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with Donidalorsen.
measure: Peak plasma Concentration (Cmax) of Donidalorsen
time frame: Up to 176 days
description: Maximum Donidalorsen plasma concentration, Cmax (ug/mL) will be assessed following SC administration
measure: Time to peak plasma Concentration (Tmax) of Donidalorsen
time frame: Up to 176 days
description: Time to peak Donidalorsen plasma concentration, Tmax (hours) will be assessed following SC administration
measure: Effects of Donidalorsen on plasma PKK concentration
time frame: Up to 176 days
description: Effects of Donidalorsen on plasma PKK concentration after multiple doses of Donidalorsen compared to baseline
arm group label: Donidalorsen
arm group type: Experimental
description: Ascending single and multiple doses of Donidalorsen administered subcutaneously
arm group label: Placebo (sterile saline 0.9%)
arm group type: Placebo Comparator
description: Calculated volume to match active comparator
intervention type: Drug
intervention name: Placebo
description: Saline .9%
arm group label: Placebo (sterile saline 0.9%)
intervention type: Drug
intervention name: Donidalorsen
description: Donidalorsen administered subcutaneously
arm group label: Donidalorsen
other name: ISIS 721744
other name: IONIS-PKK-LRx
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Canada
responsible party type: Sponsor