<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/NCT02205814</url>
  </required_header>
  <id_info>
    <org_study_id>BKOS-04</org_study_id>
    <secondary_id>2013-004999-35</secondary_id>
    <nct_id>NCT02205814</nct_id>
  </id_info>
  <brief_title>Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee</brief_title>
  <acronym>ALBATROSS-3</acronym>
  <official_title>A Double-blind, Randomised, Placebo-controlled, Four Parallel Arm, Dose-finding Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Single Intra-articular Injections of Fasitibant in Patients With Symptomatic Osteoarthritis of the Knee.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Menarini Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Menarini Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed as a double-blind, randomised, placebo-controlled, four parallel arm,&#xD;
      dose-finding study, to be conducted in approximately 26 sites, to evaluate the efficacy,&#xD;
      safety, tolerability, and pharmacokinetics of single intra-articular (IA) injections of&#xD;
      fasitibant in patients with symptomatic osteoarthritis (OA) of the knee.&#xD;
&#xD;
      Approximately 400 male and female patients 40-80 years old, with BMI &lt; 30 kg/m² and with a&#xD;
      clinical diagnosis of symptomatic primary osteoarthritis of the knee will be randomised to a&#xD;
      total of 4 treatment arms. Each arm includes a single intra-articular injection of one of&#xD;
      three dosages of fasitibant (low, intermediate and high dose) OR placebo. The randomisation&#xD;
      ratio will be 1:1:1:1.&#xD;
&#xD;
      The primary efficacy variable will be the change of the Western Ontario and McMaster&#xD;
      Universities Visual Analogue Scale 3.1 A (WOMAC VA 3.1 A) (total pain) subscore from baseline&#xD;
      up to 2 weeks after randomisation. Safety will be assessed by monitoring adverse events and&#xD;
      clinical laboratory tests; local tolerability at the injection site will also be assessed. In&#xD;
      addition, the population pharmacokinetics and the exposure-response relationship will be&#xD;
      evaluated.&#xD;
&#xD;
      The individual experimental clinical phase will last up to maximal 15 weeks encompassing 7&#xD;
      planned visits at site, including screening, randomisation, 4 follow-up visits and the End of&#xD;
      study visit.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in WOMAC A</measure>
    <time_frame>from baseline up to 2 weeks after randomisation</time_frame>
    <description>The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in WOMAC INDEX</measure>
    <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
    <description>The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder Rate According to OMERACT-OARSI Criteria</measure>
    <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
    <description>Percentage of responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria (OMERACT-OARSI criteria). Patients with at least 50 % improvement in pain or in function scores are considered responders. Alternatively, patients are considered responders if they show at least 20% improvement in at least two of the following scores: pain, function and Patients's Global Assessment (PGA) scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate</measure>
    <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
    <description>Response based on change ≥ 20 % from baseline for EQ-5D-5L index value</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">436</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Fasitibant low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: solution for intra-articular injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fasitibant intermediate dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: solution for intra-articular injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fasitibant high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: solution for intra-articular injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PLACEBO</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug: solution for intra-articular injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fasitibant- low dose</intervention_name>
    <description>Single intra-articular injection of low dose of fasitibant</description>
    <arm_group_label>Fasitibant low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fasitibant- intermediate dose</intervention_name>
    <description>Single intra-articular injection of intermediate dose of fasitibant</description>
    <arm_group_label>Fasitibant intermediate dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fasitibant- high dose</intervention_name>
    <description>Single intra-articular injection of high dose of fasitibant</description>
    <arm_group_label>Fasitibant high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo comparator</intervention_name>
    <description>Single intra-articular injection of placebo</description>
    <arm_group_label>PLACEBO</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients aged 40 to 80 years with BMI &lt; 30 kg/m²&#xD;
&#xD;
          -  Patient with Kellgren-Lawrence Grade 2 to 3, symptomatic primary osteoarthritis at the&#xD;
             index knee (ACR criteria), for which an IA treatment is indicated&#xD;
&#xD;
          -  Pain of moderate to severe intensity, even if treated with chronic doses of non&#xD;
             steroidal antinflammatory drugs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity/allergy to drugs including paracetamol and to&#xD;
             disinfectants&#xD;
&#xD;
          -  Any pharmacological treatment of concomitant disease(s) started or changed during 4&#xD;
             weeks prior to randomisation, or likely to be changed during the course of the study&#xD;
&#xD;
          -  Use of systemic or topical corticosteroids &gt; 10 mg prednisolone equivalent per day, or&#xD;
             immunosuppressant drugs&#xD;
&#xD;
          -  Current use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics,&#xD;
             antidepressive agents), including topical treatments&#xD;
&#xD;
          -  Viscosupplementation to the target knee administered &lt; 4 months prior to randomisation&#xD;
             and/or scheduled during the course of the study&#xD;
&#xD;
          -  Evidence of clinically significant hepatic disease or of moderate or severe renal&#xD;
             insufficiency&#xD;
&#xD;
          -  Current use of any medications that are substrate of CYP3A4 and/or moderate or strong&#xD;
             CYP3A4 inhibitors&#xD;
&#xD;
          -  Patients with any clinically relevant or unstable disease, or malignant neoplasms&#xD;
             that, in the opinion of the Investigator, may pose the patient at risk, or confound&#xD;
             the efficacy and safety results of the study&#xD;
&#xD;
          -  Patients with any clinically relevant abnormal safety laboratory test results, and/or&#xD;
             abnormalities in vital signs, and/or ECG parameters&#xD;
&#xD;
          -  Pregnant and breastfeeding women&#xD;
&#xD;
          -  Any sign of significant immunodeficiency, systemic infection, knee infection or knee&#xD;
             bursitis&#xD;
&#xD;
          -  Patients with bleeding diathesis or on therapy with anticoagulants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karel Pavelka, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tucson Orthopaedic Institute</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Orthopaedic Consultants</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avail Clinical Research, LLC</name>
      <address>
        <city>Deland</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbus Clinical Research</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blair Orthopaedic Associates</name>
      <address>
        <city>Altoona</city>
        <state>Pennsylvania</state>
        <zip>16602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tekton Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physicians Research Options, LLC</name>
      <address>
        <city>Draper</city>
        <state>Utah</state>
        <zip>84020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spokan Joint Replacement Center</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Revmatologie s.r.o.</name>
      <address>
        <city>Brno</city>
        <zip>638 00</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Rheumatology, Charles University Faculty Hospital</name>
      <address>
        <city>Prague</city>
        <zip>128 50</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MEDICAL PLUS s.r.o</name>
      <address>
        <city>Uherske Hradiste</city>
        <zip>686 01</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research GmbH, Research Centre Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>1262</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research GmbH, Research Centre Bochum</name>
      <address>
        <city>Bochum</city>
        <zip>44787</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research GmbH, Research Centre Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Hamburg GmbH</name>
      <address>
        <city>Hamburg</city>
        <zip>22143</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Synexus Clinical Research GmbH, Research Centre Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AmBeNet GmbH</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <state>Tuscany</state>
        <zip>50139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale</name>
      <address>
        <city>Cona</city>
        <zip>44124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Galateo U.O. di Reumatologia</name>
      <address>
        <city>Lecce</city>
        <zip>73016</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Fornaroli/Unità Complessa di Reumatologia</name>
      <address>
        <city>Magenta</city>
        <zip>20013</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Luigi Sacco, Azienda Ospedaliera, Polo Universitario/Unità Operativa Complessa di Reumatologia</name>
      <address>
        <city>Milano</city>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche</name>
      <address>
        <city>Perugia</city>
        <zip>06122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Ricerche Cliniche di Verona</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czech Republic</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <results_first_submitted>July 6, 2015</results_first_submitted>
  <results_first_submitted_qc>August 17, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 16, 2015</results_first_posted>
  <last_update_submitted>October 2, 2015</last_update_submitted>
  <last_update_submitted_qc>October 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteoarthritis, Knee</keyword>
  <keyword>Arthritis</keyword>
  <keyword>WOMAC</keyword>
  <keyword>Injections, intra-articular</keyword>
  <keyword>Fasitibant</keyword>
  <keyword>MEN 16132</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>(4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The first patient was screened on 28th April 2014. The first patient was randomised on 6th May 2014. The last patient completed the study on 6th January 2015.&#xD;
The study was conducted in 25 study sites in Czech Republic, Germany, Italy and US.</recruitment_details>
      <pre_assignment_details>A total of 645 patients entered a 2-week Screening period (including wash out); 209 of them were screen failed. One patient randomised to PLACEBO did not receive the study treatment (counted for ITT but not in safety population). Five patients received the study treatment without randomisation (not counted for ITT, but in safety population).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Fasitibant Low Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
        </group>
        <group group_id="P2">
          <title>Fasitibant Intermediate Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
        </group>
        <group group_id="P3">
          <title>Fasitibant High Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
        </group>
        <group group_id="P4">
          <title>PLACEBO</title>
          <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
                <participants group_id="P2" count="110"/>
                <participants group_id="P3" count="108"/>
                <participants group_id="P4" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
                <participants group_id="P2" count="109"/>
                <participants group_id="P3" count="103"/>
                <participants group_id="P4" count="104"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>not compliant with study procedures</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline analysis was performed on the ITT-population (n=431). The ITT-population included all patients randomised via IXRS.</population>
      <group_list>
        <group group_id="B1">
          <title>Fasitibant Low Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
        </group>
        <group group_id="B2">
          <title>Fasitibant Intermediate Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
        </group>
        <group group_id="B3">
          <title>Fasitibant High Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
        </group>
        <group group_id="B4">
          <title>PLACEBO</title>
          <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="108"/>
            <count group_id="B2" value="108"/>
            <count group_id="B3" value="107"/>
            <count group_id="B4" value="108"/>
            <count group_id="B5" value="431"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Age</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.3" spread="7.61"/>
                    <measurement group_id="B2" value="63.2" spread="8.73"/>
                    <measurement group_id="B3" value="64.7" spread="8.43"/>
                    <measurement group_id="B4" value="64.4" spread="8.50"/>
                    <measurement group_id="B5" value="64.4" spread="8.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="66"/>
                    <measurement group_id="B5" value="263"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="42"/>
                    <measurement group_id="B5" value="168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="107"/>
                    <measurement group_id="B2" value="108"/>
                    <measurement group_id="B3" value="106"/>
                    <measurement group_id="B4" value="106"/>
                    <measurement group_id="B5" value="427"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.1" spread="2.12"/>
                    <measurement group_id="B2" value="26.5" spread="2.83"/>
                    <measurement group_id="B3" value="27.1" spread="2.35"/>
                    <measurement group_id="B4" value="27.0" spread="2.60"/>
                    <measurement group_id="B5" value="26.9" spread="2.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>WOMAC A</title>
          <description>The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="286.5" spread="40.4"/>
                    <measurement group_id="B2" value="282.7" spread="40.08"/>
                    <measurement group_id="B3" value="278.3" spread="38.11"/>
                    <measurement group_id="B4" value="275.5" spread="39.81"/>
                    <measurement group_id="B5" value="280.8" spread="39.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>WOMAC INDEX</title>
          <description>The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1321.5" spread="278.88"/>
                    <measurement group_id="B2" value="1275.4" spread="283.60"/>
                    <measurement group_id="B3" value="1282.6" spread="274.50"/>
                    <measurement group_id="B4" value="1293.5" spread="239.73"/>
                    <measurement group_id="B5" value="1293.3" spread="269.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EQ VAS</title>
          <description>The EQ visual analogue scale (EQ VAS) recorded the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' on top (equal to 100) and 'the worst health you can imagine' at the bottom (equal to 0).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.1" spread="20.54"/>
                    <measurement group_id="B2" value="64.3" spread="17.21"/>
                    <measurement group_id="B3" value="67.4" spread="18.18"/>
                    <measurement group_id="B4" value="65.7" spread="19.47"/>
                    <measurement group_id="B5" value="65.1" spread="18.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in WOMAC A</title>
        <description>The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.</description>
        <time_frame>from baseline up to 2 weeks after randomisation</time_frame>
        <population>The primary efficacy analysis was performed on the ITT-population (n=431).</population>
        <group_list>
          <group group_id="O1">
            <title>Fasitibant Low Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
          </group>
          <group group_id="O2">
            <title>Fasitibant Intermediate Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
          </group>
          <group group_id="O3">
            <title>Fasitibant High Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
          </group>
          <group group_id="O4">
            <title>PLACEBO</title>
            <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in WOMAC A</title>
          <description>The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.</description>
          <population>The primary efficacy analysis was performed on the ITT-population (n=431).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
                <count group_id="O2" value="108"/>
                <count group_id="O3" value="107"/>
                <count group_id="O4" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-91.8" spread="101.85"/>
                    <measurement group_id="O2" value="-110.0" spread="99.48"/>
                    <measurement group_id="O3" value="-109.8" spread="94.65"/>
                    <measurement group_id="O4" value="-93.7" spread="94.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-106.1" spread="101.88"/>
                    <measurement group_id="O2" value="-131.5" spread="96.41"/>
                    <measurement group_id="O3" value="-115.9" spread="104.61"/>
                    <measurement group_id="O4" value="-117.2" spread="90.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>Fourhundred evaluable patients were supposed to provide approximately 80% power in rejecting the null hypothesis of equality between any dose of fasitibant and placebo based on previous results and an overall significance level of 5% (two-sided).</p_value_desc>
            <method>mixed linear model for repeated measures</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in WOMAC INDEX</title>
        <description>The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden.</description>
        <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
        <population>The secondary efficacy analysis was performed on the ITT population (n=431).</population>
        <group_list>
          <group group_id="O1">
            <title>Fasitibant Low Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
          </group>
          <group group_id="O2">
            <title>Fasitibant Intermediate Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
          </group>
          <group group_id="O3">
            <title>Fasitibant High Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
          </group>
          <group group_id="O4">
            <title>PLACEBO</title>
            <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in WOMAC INDEX</title>
          <description>The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden.</description>
          <population>The secondary efficacy analysis was performed on the ITT population (n=431).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
                <count group_id="O2" value="108"/>
                <count group_id="O3" value="107"/>
                <count group_id="O4" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-396.0" spread="464.24"/>
                    <measurement group_id="O2" value="-460.5" spread="469.68"/>
                    <measurement group_id="O3" value="-445.2" spread="424.07"/>
                    <measurement group_id="O4" value="-413.2" spread="452.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-448.0" spread="477.95"/>
                    <measurement group_id="O2" value="-563.0" spread="456.71"/>
                    <measurement group_id="O3" value="-488.7" spread="480.39"/>
                    <measurement group_id="O4" value="-517.7" spread="440.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-516.4" spread="513.70"/>
                    <measurement group_id="O2" value="-628.4" spread="500.17"/>
                    <measurement group_id="O3" value="-493.4" spread="513.94"/>
                    <measurement group_id="O4" value="-562.3" spread="487.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-566.3" spread="525.63"/>
                    <measurement group_id="O2" value="-653.8" spread="516.31"/>
                    <measurement group_id="O3" value="-547.6" spread="522.37"/>
                    <measurement group_id="O4" value="-581.3" spread="503.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>All secondary efficacy variables were analysed on the ITT population only. Multiplicity was adjusted using the Hochberg procedure. The continuous secondary efficacy variables were analysed over time and were treated in the same way as the primary efficacy variable with respective output.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>Fourhundred evaluable patients were supposed to provide approximately 80% power in rejecting the null hypothesis of equality between any dose of fasitibant and placebo based on previous results and an overall significance level of 5% (two-sided).</p_value_desc>
            <method>mixed linear model for repeated measures</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Rate According to OMERACT-OARSI Criteria</title>
        <description>Percentage of responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria (OMERACT-OARSI criteria). Patients with at least 50 % improvement in pain or in function scores are considered responders. Alternatively, patients are considered responders if they show at least 20% improvement in at least two of the following scores: pain, function and Patients's Global Assessment (PGA) scores.</description>
        <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
        <population>The secondary efficacy variables were analysed in the ITT population (n=431).</population>
        <group_list>
          <group group_id="O1">
            <title>Fasitibant Low Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
          </group>
          <group group_id="O2">
            <title>Fasitibant Intermediate Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
          </group>
          <group group_id="O3">
            <title>Fasitibant High Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
          </group>
          <group group_id="O4">
            <title>PLACEBO</title>
            <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Rate According to OMERACT-OARSI Criteria</title>
          <description>Percentage of responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria (OMERACT-OARSI criteria). Patients with at least 50 % improvement in pain or in function scores are considered responders. Alternatively, patients are considered responders if they show at least 20% improvement in at least two of the following scores: pain, function and Patients's Global Assessment (PGA) scores.</description>
          <population>The secondary efficacy variables were analysed in the ITT population (n=431).</population>
          <units>percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
                <count group_id="O2" value="108"/>
                <count group_id="O3" value="107"/>
                <count group_id="O4" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.9"/>
                    <measurement group_id="O2" value="56.5"/>
                    <measurement group_id="O3" value="63.6"/>
                    <measurement group_id="O4" value="55.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.3"/>
                    <measurement group_id="O2" value="72.2"/>
                    <measurement group_id="O3" value="62.6"/>
                    <measurement group_id="O4" value="68.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.7"/>
                    <measurement group_id="O2" value="72.2"/>
                    <measurement group_id="O3" value="65.4"/>
                    <measurement group_id="O4" value="66.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.3"/>
                    <measurement group_id="O2" value="74.1"/>
                    <measurement group_id="O3" value="67.3"/>
                    <measurement group_id="O4" value="67.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate</title>
        <description>Response based on change ≥ 20 % from baseline for EQ-5D-5L index value</description>
        <time_frame>from baseline up to 6 weeks after randomisation</time_frame>
        <population>The secondary efficacy analysis was performed on the ITT-population (n=431).</population>
        <group_list>
          <group group_id="O1">
            <title>Fasitibant Low Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
          </group>
          <group group_id="O2">
            <title>Fasitibant Intermediate Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
          </group>
          <group group_id="O3">
            <title>Fasitibant High Dose</title>
            <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
          </group>
          <group group_id="O4">
            <title>PLACEBO</title>
            <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate</title>
          <description>Response based on change ≥ 20 % from baseline for EQ-5D-5L index value</description>
          <population>The secondary efficacy analysis was performed on the ITT-population (n=431).</population>
          <units>percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
                <count group_id="O2" value="108"/>
                <count group_id="O3" value="107"/>
                <count group_id="O4" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 2 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5"/>
                    <measurement group_id="O2" value="18.5"/>
                    <measurement group_id="O3" value="20.6"/>
                    <measurement group_id="O4" value="24.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 after randomisation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1"/>
                    <measurement group_id="O2" value="27.8"/>
                    <measurement group_id="O3" value="25.2"/>
                    <measurement group_id="O4" value="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>For all patients receiving the study treatment (safety population, N=435), adverse event data were collected over a period of maximal 15 weeks.</time_frame>
      <desc>An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Fasitibant Low Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- low dose: Single intra-articular injection of low dose of fasitibant</description>
        </group>
        <group group_id="E2">
          <title>Fasitibant Intermediate Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- intermediate dose: Single intra-articular injection of intermediate dose of fasitibant</description>
        </group>
        <group group_id="E3">
          <title>Fasitibant High Dose</title>
          <description>Drug: solution for intra-articular injection&#xD;
Fasitibant- high dose: Single intra-articular injection of high dose of fasitibant</description>
        </group>
        <group group_id="E4">
          <title>PLACEBO</title>
          <description>Drug: solution for intra-articular injection&#xD;
Placebo comparator: Single intra-articular injection of placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer female</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Laryngeal oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Hernia repair</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Knee arthroplasty</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Malignant breast lump removal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="110"/>
                <counts group_id="E2" subjects_affected="46" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="36" subjects_at_risk="108"/>
                <counts group_id="E4" subjects_affected="44" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="110"/>
                <counts group_id="E2" events="18" subjects_affected="17" subjects_at_risk="110"/>
                <counts group_id="E3" events="11" subjects_affected="11" subjects_at_risk="108"/>
                <counts group_id="E4" events="13" subjects_affected="13" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="110"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="110"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E4" events="8" subjects_affected="8" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="110"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="110"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="107"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Prior to submitting the results of this study for publication or presentation, the Investigator will allow the sponsor at least 30 days time to review and comment upon the publication manuscript. It is agreed, that the results of the study will not be submitted for presentation, abstract, poster exhibition, or publication by the investigator until the sponsor has reviewed/commented and agreed to any publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Angela Capriati, MD PhD - Corporate Director Clinical Research</name_or_title>
      <organization>MENARINI Group</organization>
      <phone>+39 055 5680 ext 9990</phone>
      <email>acapriati@menarini-ricerche.it</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02205814
org study id: BKOS-04
secondary id: 2013-004999-35
nct id: NCT02205814
lead sponsor: 
has dmc: No
This study is designed as a double-blind, randomised, placebo-controlled, four parallel arm,
      dose-finding study, to be conducted in approximately 26 sites, to evaluate the efficacy,
      safety, tolerability, and pharmacokinetics of single intra-articular (IA) injections of
      fasitibant in patients with symptomatic osteoarthritis (OA) of the knee.

      Approximately 400 male and female patients 40-80 years old, with BMI < 30 kg/m² and with a
      clinical diagnosis of symptomatic primary osteoarthritis of the knee will be randomised to a
      total of 4 treatment arms. Each arm includes a single intra-articular injection of one of
      three dosages of fasitibant (low, intermediate and high dose) OR placebo. The randomisation
      ratio will be 1:1:1:1.

      The primary efficacy variable will be the change of the Western Ontario and McMaster
      Universities Visual Analogue Scale 3.1 A (WOMAC VA 3.1 A) (total pain) subscore from baseline
      up to 2 weeks after randomisation. Safety will be assessed by monitoring adverse events and
      clinical laboratory tests; local tolerability at the injection site will also be assessed. In
      addition, the population pharmacokinetics and the exposure-response relationship will be
      evaluated.

      The individual experimental clinical phase will last up to maximal 15 weeks encompassing 7
      planned visits at site, including screening, randomisation, 4 follow-up visits and the End of
      study visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in WOMAC A
time frame: from baseline up to 2 weeks after randomisation
description: The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.
measure: Change in WOMAC INDEX
time frame: from baseline up to 6 weeks after randomisation
description: The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden.
measure: Responder Rate According to OMERACT-OARSI Criteria
time frame: from baseline up to 6 weeks after randomisation
description: Percentage of responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria (OMERACT-OARSI criteria). Patients with at least 50 % improvement in pain or in function scores are considered responders. Alternatively, patients are considered responders if they show at least 20% improvement in at least two of the following scores: pain, function and Patients's Global Assessment (PGA) scores.
measure: Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate
time frame: from baseline up to 6 weeks after randomisation
description: Response based on change ≥ 20 % from baseline for EQ-5D-5L index value
arm group label: Fasitibant low dose
arm group type: Experimental
description: Drug: solution for intra-articular injection
arm group label: Fasitibant intermediate dose
arm group type: Experimental
description: Drug: solution for intra-articular injection
arm group label: Fasitibant high dose
arm group type: Experimental
description: Drug: solution for intra-articular injection
arm group label: PLACEBO
arm group type: Placebo Comparator
description: Drug: solution for intra-articular injection
intervention type: Drug
intervention name: Fasitibant- low dose
description: Single intra-articular injection of low dose of fasitibant
arm group label: Fasitibant low dose
intervention type: Drug
intervention name: Fasitibant- intermediate dose
description: Single intra-articular injection of intermediate dose of fasitibant
arm group label: Fasitibant intermediate dose
intervention type: Drug
intervention name: Fasitibant- high dose
description: Single intra-articular injection of high dose of fasitibant
arm group label: Fasitibant high dose
intervention type: Drug
intervention name: Placebo comparator
description: Single intra-articular injection of placebo
arm group label: PLACEBO
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Karel Pavelka, Professor
role: Study Chair
affiliation: Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czech Republic
country: Germany
country: Italy
country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: (4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 