<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/NCT03005873</url>
  </required_header>
  <id_info>
    <org_study_id>TLC599A2003</org_study_id>
    <nct_id>NCT03005873</nct_id>
  </id_info>
  <brief_title>Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for TLC599 in OA Patients</brief_title>
  <official_title>A Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for Single Dose Administration of TLC599 in Patients With Osteoarthritis (OA) of Knee</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taiwan Liposome Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taiwan Liposome Company</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is a Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study&#xD;
      to investigate the safety and efficacy of TLC599 in subjects with osteoarthritis of the knee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol No: TLC599A2003 Name of Finished Product: TLC599&#xD;
&#xD;
      Title of Study:&#xD;
&#xD;
      A Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study for Single&#xD;
      dose Administration of TLC599 in Patients with Osteoarthritis (OA) of Knee.&#xD;
&#xD;
      Study duration:&#xD;
&#xD;
      The trial will last around 27 weeks including a 21-day screening period and a 24-week&#xD;
      follow-up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 16, 2017</start_date>
  <completion_date type="Actual">July 4, 2018</completion_date>
  <primary_completion_date type="Actual">July 4, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>WOMAC questionnaire pain sub-scale</measure>
    <time_frame>from dosing through Week 12</time_frame>
    <description>The primary endpoint is to evaluate the change from baseline by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale through Week 12.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>WOMAC questionnaire pain sub-scale</measure>
    <time_frame>at Weeks 1, 4, 8, 12, 16, 20, and 24</time_frame>
    <description>Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in pain / function subscales of WOMAC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score (VAS)</measure>
    <time_frame>at Weeks 1, 4, 8, 12, 16, 20, and 24</time_frame>
    <description>Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score (VAS)</measure>
    <time_frame>from dosing through Week 12, 16, 20, 24</time_frame>
    <description>Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC questionnaire pain sub-scale</measure>
    <time_frame>from dosing through Week 12, 16, 20, 24</time_frame>
    <description>Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol-5 Dimension questionnaire</measure>
    <time_frame>at Weeks 1, 4, 8, 12, 16, 20, and 24</time_frame>
    <description>Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in EuroQol-5 Dimension questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Usage of acetaminophen</measure>
    <time_frame>at Weeks 1, 4, 8, 12, 16, 20, and 24</time_frame>
    <description>Total consumption of acetaminophen at Weeks 1, 4, 8, 12, 16, 20, and 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>up to 24 weeks after dosing</time_frame>
    <description>To evaluate the safety and tolerability of TLC599 by incidence of Treatment-Emergent Adverse Events reported by Investigators</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">77</enrollment>
  <condition>Osteoarthritis of the Knee</condition>
  <arm_group>
    <arm_group_label>TLC599 LD group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 mg DSP with 100 µmol PL (1.0 mL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TLC599 HD group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>18 mg DSP with 150 µmol PL (1.5 mL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1.5 mL normal saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TLC599 LD group</intervention_name>
    <description>Single dose via intra-articular injection</description>
    <arm_group_label>TLC599 LD group</arm_group_label>
    <other_name>12 mg DSP with 100 µmol PL (1.0 mL)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>Single dose via intra-articular injection</description>
    <arm_group_label>Placebo group</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TLC599 HD group</intervention_name>
    <description>Single dose via intra-articular injection</description>
    <arm_group_label>TLC599 HD group</arm_group_label>
    <other_name>18 mg DSP with 150 µmol PL (1.5 mL)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients, at least 50 years of age.&#xD;
&#xD;
          2. Documented diagnosis of OA of the knee for at least 6 months&#xD;
&#xD;
          3. The study knee has OA with Grade 2 to 3 severity based on the Kellgren Lawrence grades&#xD;
&#xD;
          4. Patients with patient related visual analogue scale (VAS) score of 5.0 to 9.0 at&#xD;
             baseline.&#xD;
&#xD;
          5. Willing and able to comply with study procedures and provide written informed consent.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          1. Patients who received systemic corticosteroids within the last 30 days prior to&#xD;
             dosing.&#xD;
&#xD;
          2. Patients who use prohibited medications within 7 days prior to study drug&#xD;
             administration or any pain control medication including acetaminophen within 48 hours&#xD;
             prior to study drug administration.&#xD;
&#xD;
          3. Patients who use prohibited medications other than acetaminophen and oral NSAIDs from&#xD;
             screening visit to 7 days prior to study drug administration.&#xD;
&#xD;
          4. Documented history and confirmed autoimmune disease&#xD;
&#xD;
          5. History of post-traumatic knee arthritis, or evidence of intra articular bleeding of&#xD;
             the study knee&#xD;
&#xD;
          6. History of infective arthritis&#xD;
&#xD;
          7. Unstable study knee joint&#xD;
&#xD;
          8. Use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee&#xD;
             within 3 months prior to the screening visit.&#xD;
&#xD;
          9. A history of treated malignancy which is disease free for ≤ 5 years prior to the&#xD;
             screening visit&#xD;
&#xD;
         10. Uncontrolled and unstable concurrent medical or psychiatric illness, that will&#xD;
             jeopardize the safety of the patient&#xD;
&#xD;
         11. Use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory&#xD;
             diseases within 6 months prior to the screening visit.&#xD;
&#xD;
         12. Current use of anticoagulants, including warfarin, heparin, low molecular weight&#xD;
             heparin, or dabigatran.&#xD;
&#xD;
         13. Abnormalities of laboratory parameters as described below will qualify for exclusion:&#xD;
&#xD;
               -  hemoglobin &lt; 8 g/dL;&#xD;
&#xD;
               -  total white blood cell count &lt; 4000/ µL;&#xD;
&#xD;
               -  serum bilirubin/ alanine aminotransferase/ aspartate aminotransferase &gt; 2 times&#xD;
                  upper limit of normal (ULN) for the laboratory reference ranges;&#xD;
&#xD;
               -  serum creatinine &gt; 2 times ULN for the laboratory reference range;&#xD;
&#xD;
               -  serum uric acid &gt; ULN for the laboratory reference range;&#xD;
&#xD;
               -  prothrombin time/International Normalized Ratio &gt; ULN for the laboratory&#xD;
                  reference range.&#xD;
&#xD;
         14. Contraindication to undergoing magnetic resonance imaging (MRI)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yvonne Shih, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Taiwan Liposome Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Genesis Research Services Pty Limited</name>
      <address>
        <city>Broadmeadow</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pendlebury Clinic Private Hospital</name>
      <address>
        <city>Cardiff</city>
        <zip>2285</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Footscray Hospital- Western Health</name>
      <address>
        <city>Footscray</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research Limited</name>
      <address>
        <city>Nedlands,</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>Sydney</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Show Chwan Memorial Hospital</name>
      <address>
        <city>Changhua</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Medical University Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chung Shan Medical University Hosptial</name>
      <address>
        <city>Taichung</city>
        <zip>402</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cheng Hsin General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shin Kong Wu Ho-Su Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical Universtiy Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>December 12, 2016</study_first_submitted>
  <study_first_submitted_qc>December 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>September 17, 2018</last_update_submitted>
  <last_update_submitted_qc>September 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>osteoarthritis of the knee</keyword>
  <keyword>TLC599</keyword>
  <keyword>Dexamethasone</keyword>
  <keyword>DSP</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 24, 2021</submitted>
    <returned>December 27, 2021</returned>
    <submitted>May 5, 2022</submitted>
    <returned>January 31, 2023</returned>
  </pending_results>
  <!-- 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/NCT03005873
org study id: TLC599A2003
nct id: NCT03005873
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This trial is a Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study
      to investigate the safety and efficacy of TLC599 in subjects with osteoarthritis of the knee.
Protocol No: TLC599A2003 Name of Finished Product: TLC599

      Title of Study:

      A Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study for Single
      dose Administration of TLC599 in Patients with Osteoarthritis (OA) of Knee.

      Study duration:

      The trial will last around 27 weeks including a 21-day screening period and a 24-week
      follow-up period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: WOMAC questionnaire pain sub-scale
time frame: from dosing through Week 12
description: The primary endpoint is to evaluate the change from baseline by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale through Week 12.
measure: WOMAC questionnaire pain sub-scale
time frame: at Weeks 1, 4, 8, 12, 16, 20, and 24
description: Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in pain / function subscales of WOMAC.
measure: Pain score (VAS)
time frame: at Weeks 1, 4, 8, 12, 16, 20, and 24
description: Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).
measure: Pain score (VAS)
time frame: from dosing through Week 12, 16, 20, 24
description: Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).
measure: WOMAC questionnaire pain sub-scale
time frame: from dosing through Week 12, 16, 20, 24
description: Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).
measure: EuroQol-5 Dimension questionnaire
time frame: at Weeks 1, 4, 8, 12, 16, 20, and 24
description: Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in EuroQol-5 Dimension questionnaire.
measure: Usage of acetaminophen
time frame: at Weeks 1, 4, 8, 12, 16, 20, and 24
description: Total consumption of acetaminophen at Weeks 1, 4, 8, 12, 16, 20, and 24.
measure: Incidence of Treatment-Emergent Adverse Events
time frame: up to 24 weeks after dosing
description: To evaluate the safety and tolerability of TLC599 by incidence of Treatment-Emergent Adverse Events reported by Investigators
arm group label: TLC599 LD group
arm group type: Experimental
description: 12 mg DSP with 100 µmol PL (1.0 mL)
arm group label: TLC599 HD group
arm group type: Experimental
description: 18 mg DSP with 150 µmol PL (1.5 mL)
arm group label: Placebo group
arm group type: Placebo Comparator
description: 1.5 mL normal saline
intervention type: Drug
intervention name: TLC599 LD group
description: Single dose via intra-articular injection
arm group label: TLC599 LD group
other name: 12 mg DSP with 100 µmol PL (1.0 mL)
intervention type: Drug
intervention name: Normal Saline
description: Single dose via intra-articular injection
arm group label: Placebo group
other name: Placebo
intervention type: Drug
intervention name: TLC599 HD group
description: Single dose via intra-articular injection
arm group label: TLC599 HD group
other name: 18 mg DSP with 150 µmol PL (1.5 mL)
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Yvonne Shih, PhD
role: Study Director
affiliation: Taiwan Liposome Company
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Taiwan
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
sharing ipd: Undecided
submitted: November 24, 2021
returned: December 27, 2021
submitted: May 5, 2022
returned: January 31, 2023