<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/NCT01668511</url>
  </required_header>
  <id_info>
    <org_study_id>M12-756</org_study_id>
    <nct_id>NCT01668511</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Injections of ABT-981 in Patients With Osteoarthritis of the Knee</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo Controlled Study in Patients With Osteoarthritis of the Knee to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of ABT-981</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie (prior sponsor, Abbott)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety, tolerability and pharmacokinetics of ABT-981 in patients with&#xD;
      osteoarthritis of the knee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose&#xD;
      study. Thirty-six patients with osteoarthritis of the knee will be selected to participate.&#xD;
      Patients will be randomized to receive either ABT-981 or placebo. ABT-981 or placebo will be&#xD;
      administered as subcutaneous (under the skin) injections in four dosing groups. Subjects will&#xD;
      be administered subcutaneous injections of ABT-981 for up to 8 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>From date of first dose of ABT-981 until 70 days after the last dose of ABT-981</time_frame>
    <description>Collect all adverse events at each visit</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical Exam including vital signs</measure>
    <time_frame>From date of first dose of ABT-981 until 70 days after last dose of ABT-981</time_frame>
    <description>Blood pressure, heart rate and body temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Lab Testing</measure>
    <time_frame>From date of first dose of ABT-981 until 70 days after the last dose of ABT-981</time_frame>
    <description>Hematology, Chemistry, and Urinalysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in Electrocardiogram (ECG)</measure>
    <time_frame>Prior to dose and 8 hours post dose on each day of dosing</time_frame>
    <description>ECGs done in triplicate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed serum concentration (Cmax) of ABT-981</measure>
    <time_frame>Prior to first dose up to 70 days after the last dose of ABT-981</time_frame>
    <description>Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Cmax (Tmax) of ABT-981</measure>
    <time_frame>Prior to first dose up to 70 days after the last dose of ABT-981</time_frame>
    <description>Time to Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The area under the time curve (AUC) of ABT-981</measure>
    <time_frame>Prior to first dose up until 70 days after the last dose of ABT-981</time_frame>
    <description>AUC</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981</measure>
    <time_frame>Prior to the last dose up to 70 days after the last dose of ABT-981</time_frame>
    <description>The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of anti-drug anti-bodies (ADA) of ABT-981</measure>
    <time_frame>Prior to each dose and up until 70 days after the last dose of ABT-981</time_frame>
    <description>Measurement of ADA</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized 7 drug/2 placebo by group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized 7 drug/2 placebo by group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized 7 drug/2 placebo by group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized 7 drug/2 placebo by group</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ABT-981</intervention_name>
    <description>Injection</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Injection</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult male or female, 40 to 70 years of age, inclusive.&#xD;
&#xD;
          -  History of symptomatic osteoarthritis (OA) of the knee joint for at least 3 months,&#xD;
             with typical Osteoarthritis (OA) symptoms&#xD;
&#xD;
          -  Radiographic Osteoarthritis (OA) of Kellgren-Lawrence (K-L) grade 1, 2 or 3&#xD;
&#xD;
          -  Patients assessment of Osteoarthritis (OA) pain intensity of the study joint is&#xD;
             between 40 and 80 on the 0 - 100 mm VAS scale&#xD;
&#xD;
          -  Other than Osteoarthritis (OA) of the study joint, patient should be in general good&#xD;
             health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Radiographic OA of Kellgren-Lawrence grade 4 or chronic opioid user due to severe knee&#xD;
             OA&#xD;
&#xD;
          -  History of allergic reaction or significant sensitivity to any constituents of the&#xD;
             study drug and acetominophen or history of anaphylactic reaction to any agent&#xD;
&#xD;
          -  Significant trauma or surgery to the study joint within the last year or arthroscopy&#xD;
             within 6 months, or, scheduled for major surgery to the study joint&#xD;
&#xD;
          -  Diagnosis of rheumatoid arthritis, other autoimmune disorders or any arthritis other&#xD;
             than Osteoarthritis (OA) of the knee.&#xD;
&#xD;
          -  Any uncontrolled medical illness including unstable treatment or therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susanne X. Wang, MD</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Site Reference ID/Investigator# 78613</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Wang SX, Abramson SB, Attur M, Karsdal MA, Preston RA, Lozada CJ, Kosloski MP, Hong F, Jiang P, Saltarelli MJ, Hendrickson BA, Medema JK. Safety, tolerability, and pharmacodynamics of an anti-interleukin-1alpha/beta dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study. Osteoarthritis Cartilage. 2017 Dec;25(12):1952-1961. doi: 10.1016/j.joca.2017.09.007. Epub 2017 Sep 28.</citation>
    <PMID>28964890</PMID>
  </results_reference>
  <verification_date>November 2013</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>November 16, 2017</last_update_submitted>
  <last_update_submitted_qc>November 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunogenicity</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Osteoarthritis</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</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/NCT01668511
org study id: M12-756
nct id: NCT01668511
lead sponsor: 
has dmc: No
To assess the safety, tolerability and pharmacokinetics of ABT-981 in patients with
      osteoarthritis of the knee.
This is a phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose
      study. Thirty-six patients with osteoarthritis of the knee will be selected to participate.
      Patients will be randomized to receive either ABT-981 or placebo. ABT-981 or placebo will be
      administered as subcutaneous (under the skin) injections in four dosing groups. Subjects will
      be administered subcutaneous injections of ABT-981 for up to 8 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of participants with Adverse Events
time frame: From date of first dose of ABT-981 until 70 days after the last dose of ABT-981
description: Collect all adverse events at each visit
measure: Physical Exam including vital signs
time frame: From date of first dose of ABT-981 until 70 days after last dose of ABT-981
description: Blood pressure, heart rate and body temperature
measure: Clinical Lab Testing
time frame: From date of first dose of ABT-981 until 70 days after the last dose of ABT-981
description: Hematology, Chemistry, and Urinalysis
measure: Change from Baseline in Electrocardiogram (ECG)
time frame: Prior to dose and 8 hours post dose on each day of dosing
description: ECGs done in triplicate
measure: Maximum observed serum concentration (Cmax) of ABT-981
time frame: Prior to first dose up to 70 days after the last dose of ABT-981
description: Cmax
measure: Time to Cmax (Tmax) of ABT-981
time frame: Prior to first dose up to 70 days after the last dose of ABT-981
description: Time to Cmax
measure: The area under the time curve (AUC) of ABT-981
time frame: Prior to first dose up until 70 days after the last dose of ABT-981
description: AUC
measure: The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981
time frame: Prior to the last dose up to 70 days after the last dose of ABT-981
description: The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981
measure: Measurement of anti-drug anti-bodies (ADA) of ABT-981
time frame: Prior to each dose and up until 70 days after the last dose of ABT-981
description: Measurement of ADA
arm group label: Group 1
arm group type: Experimental
description: Randomized 7 drug/2 placebo by group
arm group label: Group 2
arm group type: Experimental
description: Randomized 7 drug/2 placebo by group
arm group label: Group 3
arm group type: Experimental
description: Randomized 7 drug/2 placebo by group
arm group label: Group 4
arm group type: Experimental
description: Randomized 7 drug/2 placebo by group
intervention type: Biological
intervention name: ABT-981
description: Injection
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
intervention type: Biological
intervention name: Placebo
description: Placebo Injection
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: No
last name: Susanne X. Wang, MD
role: Study Director
affiliation: AbbVie
facility: 
country: United States
citation: Wang SX, Abramson SB, Attur M, Karsdal MA, Preston RA, Lozada CJ, Kosloski MP, Hong F, Jiang P, Saltarelli MJ, Hendrickson BA, Medema JK. Safety, tolerability, and pharmacodynamics of an anti-interleukin-1alpha/beta dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study. Osteoarthritis Cartilage. 2017 Dec;25(12):1952-1961. doi: 10.1016/j.joca.2017.09.007. Epub 2017 Sep 28.
PMID: 28964890
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee