<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/NCT01710852</url>
  </required_header>
  <id_info>
    <org_study_id>ISIS 329993-CS6</org_study_id>
    <nct_id>NCT01710852</nct_id>
  </id_info>
  <brief_title>Antiarrhythmic and Symptomatic Effect of ISIS CRP Rx Targeting CRP in Paroxysmal Atrial Fibrillation</brief_title>
  <acronym>ASET</acronym>
  <official_title>A Phase 2 Study to Assess the Antiarrhythmic and Symptomatic Effect of the Second Generation Antisense Oligonucleotide ISIS 329993 Targeting CRP in Patients With Paroxysmal Atrial Fibrillation</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate whether treatment with ISIS CRP Rx can reduce AF&#xD;
      (Atrial Fibrillation) burden (percentage of time spent in AF) in subjects with paroxysmal AF&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AF burden reduction</measure>
    <time_frame>113 Days</time_frame>
    <description>Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the effect of ISIS CRP Rx on the:</measure>
    <time_frame>113 Days</time_frame>
    <description>total number of AF episodes&#xD;
average duration of AF per episode&#xD;
average sinus rhythm duration&#xD;
atrial and ventricular rate during AF episodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm</measure>
    <time_frame>113 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the effect of ISIS CRP Rx on measures of Quality of Life</measure>
    <time_frame>113 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess whether treatment with ISIS CRP Rx reduces hsCRP in subjects with paroxysmal AF</measure>
    <time_frame>113 Days</time_frame>
    <description>Change from Baseline will be compared for each treatment period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the safety of ISIS CRP Rx in subjects with paroxysmal AF</measure>
    <time_frame>113 Days</time_frame>
    <description>Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the tolerability of ISIS CRP Rx in subjects with paroxysmal AF</measure>
    <time_frame>113 Days</time_frame>
    <description>Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacokinetics of ISIS CRP Rx in subjects with paroxysmal AF</measure>
    <time_frame>113 Days</time_frame>
    <description>Trough levels of ISIS CRP Rx will be assessed at intervals throughout the study</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Paroxysmal Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ISIS CRP Rx followed by Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo followed by ISIS CRP Rx</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ISIS CRP Rx</intervention_name>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male of female; age over 18 years&#xD;
&#xD;
          -  Dual chamber permanent pacemaker implanted&#xD;
&#xD;
          -  Confirmed diagnosis of paroxysmal atrial fibrillation with an AF burden of 1 to 50%,&#xD;
             as derived from pacemaker diagnostic algorithms&#xD;
&#xD;
          -  Able to have pacemaker antiarrhythmic algorithms turned off for the duration of the&#xD;
             study&#xD;
&#xD;
          -  Able to discontinue all Class I and III antiarrhythmic medication for the duration of&#xD;
             the study&#xD;
&#xD;
          -  Therapeutically anticoagulated with warfarin or dabigatran, and anticipated to be for&#xD;
             duration of the study&#xD;
&#xD;
          -  High sensitivity C-Reactive Protein (hsCRP) between 2 and 10 mg/L (inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant abnormalities in medical history, physical examination, or&#xD;
             screening laboratory results that would render a subject unsuitable for inclusion&#xD;
&#xD;
          -  NYHA class III/IV heart failure&#xD;
&#xD;
          -  Impaired left ventricular function of less than 45% determined by echocardiography&#xD;
             within 3 months of screening&#xD;
&#xD;
          -  Moderate or greater mitral regurgitation assessed by echocardiography within 3 months&#xD;
             of screening&#xD;
&#xD;
          -  Permanent AF&#xD;
&#xD;
          -  Continuous Amiodarone therapy within 90 days prior to Study Day 1&#xD;
&#xD;
          -  Treatment with another Study Drug, biological agent, or device within one-month of&#xD;
             screening, or five half-lives of study agent, whichever is longer&#xD;
&#xD;
          -  Use of systemic corticosteroids or other anti-inflammatory medications including&#xD;
             non-steroidal anti-inflammatory drugs (NSAIDs)&#xD;
&#xD;
          -  Use of statins, ACE inhibitors or AT-receptor antagonists unless on a stable regimen&#xD;
             for at least 3 months prior to dosing and will remain on a stable regimen for the&#xD;
             duration of the study&#xD;
&#xD;
          -  Uncontrolled hypertension (BP &gt;160/100)&#xD;
&#xD;
          -  Current or expected use of any anticoagulant apart from warfarin or dabigatran&#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>Eastbourne General Hospital - Cardiology Department</name>
      <address>
        <city>Eastbourne</city>
        <state>East Sussex</state>
        <zip>BN21 2UD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <last_update_submitted>August 24, 2015</last_update_submitted>
  <last_update_submitted_qc>August 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 26, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Paroxysmal Atrial Fibrillation</keyword>
  <keyword>AF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</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/NCT01710852
org study id: ISIS 329993-CS6
nct id: NCT01710852
lead sponsor: 
has dmc: Yes
The purpose of this study is to evaluate whether treatment with ISIS CRP Rx can reduce AF
      (Atrial Fibrillation) burden (percentage of time spent in AF) in subjects with paroxysmal AF
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: AF burden reduction
time frame: 113 Days
description: Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring
measure: To assess the effect of ISIS CRP Rx on the:
time frame: 113 Days
description: total number of AF episodes
average duration of AF per episode
average sinus rhythm duration
atrial and ventricular rate during AF episodes
measure: To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm
time frame: 113 Days
measure: To assess the effect of ISIS CRP Rx on measures of Quality of Life
time frame: 113 Days
measure: To assess whether treatment with ISIS CRP Rx reduces hsCRP in subjects with paroxysmal AF
time frame: 113 Days
description: Change from Baseline will be compared for each treatment period
measure: To assess the safety of ISIS CRP Rx in subjects with paroxysmal AF
time frame: 113 Days
description: Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.
measure: To assess the tolerability of ISIS CRP Rx in subjects with paroxysmal AF
time frame: 113 Days
description: Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.
measure: To assess the pharmacokinetics of ISIS CRP Rx in subjects with paroxysmal AF
time frame: 113 Days
description: Trough levels of ISIS CRP Rx will be assessed at intervals throughout the study
arm group label: Group A
arm group type: Experimental
description: ISIS CRP Rx followed by Placebo
arm group label: Group B
arm group type: Experimental
description: Placebo followed by ISIS CRP Rx
intervention type: Drug
intervention name: ISIS CRP Rx
arm group label: Group A
arm group label: Group B
intervention type: Drug
intervention name: Placebo
arm group label: Group A
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Atrial Fibrillation