<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/NCT03754049</url>
  </required_header>
  <id_info>
    <org_study_id>TLC599A2004</org_study_id>
    <nct_id>NCT03754049</nct_id>
  </id_info>
  <brief_title>A Phase 2, Open Label, PK Study of TLC599 in Subject With Osteoarthritis of the Knee</brief_title>
  <official_title>A Phase 2, Open-label, Pharmacokinetic Study of a Single Intra-articular Administration of TLC599 in Subjects With Mild to Moderate Osteoarthritis of the 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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a Phase 2, open-label, 1-period, parallel study with 9 cohorts of subjects with&#xD;
      OA of the knee enrolled to receive single-dose of TLC599 or DSP via IA injection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 2, open-label, 1 period, parallel study will enroll approximately 90 subjects to&#xD;
      receive a single dose of TLC599 or DSP via IA injection, followed by a PK evaluation period&#xD;
      up to 24 weeks and an additional follow-up period of 1 to 5 weeks. Additional subjects may be&#xD;
      recruited as needed to achieve at least 10 subjects completing the 1-week blood collection&#xD;
      period for each treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Actual">June 23, 2022</completion_date>
  <primary_completion_date type="Actual">June 23, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the Curve [AUC]</measure>
    <time_frame>Baseline till 24 weeks post IP administration</time_frame>
    <description>Area under the concentration-time curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax: maximum concentration</measure>
    <time_frame>Baseline till 24 weeks post IP administration</time_frame>
    <description>Maximum concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax: time to peak concentration</measure>
    <time_frame>Baseline till 24 weeks post IP administration</time_frame>
    <description>Time to peak concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of AEs, including SAE and treatment-emergent AE</measure>
    <time_frame>Screening till 25 weeks post IP administration</time_frame>
    <description>Number of AEs, including SAE and treatment-emergent AE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cortisol concentration</measure>
    <time_frame>baseline till 24 weeks post IP administration</time_frame>
    <description>Cortisol concentration</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>OSTEOARTHRITIS OF THE KNEE</condition>
  <arm_group>
    <arm_group_label>TLC599 12 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 mg DSP with 100 μmol phospholipid via IA injection;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TLC599 6 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 mg DSP with 50 μmol phospholipid via IA injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DSP 4mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TLC599</intervention_name>
    <description>TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).</description>
    <arm_group_label>TLC599 12 mg</arm_group_label>
    <arm_group_label>TLC599 6 mg</arm_group_label>
    <other_name>TLC599 Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DSP</intervention_name>
    <description>Dexamethasone sodium phosphate (DSP) is a glucocorticoid widely used in the treatment of joint pain such as gout, osteoarthritis and rheumatoid arthritis via IA injection.</description>
    <arm_group_label>DSP 4mg</arm_group_label>
    <other_name>Dexamethasone Sodium Phosphate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female non or moderate smokers, 45 years or older, with BMI ≤ 40.0 kg/m2&#xD;
&#xD;
          2. Has symptoms associated with OA of the knee for at least 6 months prior to Screening&#xD;
             and confirmation of mild to moderate OA&#xD;
&#xD;
          3. The study knee has OA with grade 1-3 in severity based on the Kellgren-Lawrence grades&#xD;
&#xD;
          4. Females of childbearing potential to use acceptable contraceptive methods until 25&#xD;
             weeks after study drug administration&#xD;
&#xD;
          5. Male subjects must to use acceptable contraceptive methods from dosing until 25 weeks&#xD;
             after study drug administration&#xD;
&#xD;
          6. Willing and able to comply with study procedures and provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically significant abnormality at physical examination, laboratory test results or&#xD;
             positive test for hepatitis B, hepatitis C, or HIV&#xD;
&#xD;
          2. Positive urine drug screen&#xD;
&#xD;
          3. History of allergic reactions to TLC599, its components or other related drugs&#xD;
&#xD;
          4. Clinically significant and unstable illness&#xD;
&#xD;
          5. History of clinically significant autoimmune disease&#xD;
&#xD;
          6. Evidence of intra articular bleeding of the study knee&#xD;
&#xD;
          7. History of infective arthritis or suspected / concurrent infection in the study knee;&#xD;
             clinical symptoms and signs of acute infection or infection-related inflammation in&#xD;
             the non-study knee&#xD;
&#xD;
          8. Skin lesion/breakdown at the anticipated injection site or any condition that would&#xD;
             impair penetration of the study knee joint space.&#xD;
&#xD;
          9. Blood coagulation disorders&#xD;
&#xD;
         10. Total white blood cell count &lt;4000/ μL or &gt;13000/ μL&#xD;
&#xD;
         11. History of acquired or congenital immunodeficiency diseases&#xD;
&#xD;
         12. History of treated malignancy which is disease free for ≤ 5 years&#xD;
&#xD;
         13. Stroke or myocardial infarction within 3 months&#xD;
&#xD;
         14. Subjects with a condition or in a situation which will interfere with the subject's&#xD;
             ability to comply or cooperate with the dosing and visit schedules and the protocol&#xD;
             evaluations or may not be suitable for this study&#xD;
&#xD;
         15. Clinically significant ECG abnormalities or vital sign abnormalities&#xD;
&#xD;
         16. Poorly controlled hypertension or vital sign abnormalities&#xD;
&#xD;
         17. History of significant alcohol abuse within one year or regular use of alcohol within&#xD;
             six months&#xD;
&#xD;
         18. History of significant drug abuse within one year or use of soft drugs within 3 months&#xD;
             or hard drugs within 1 year&#xD;
&#xD;
         19. Participation in a clinical research study involving the administration of an&#xD;
             investigational or marketed drug or device within 30 days, administration of a&#xD;
             biological product in the context of a clinical research study within 90 days&#xD;
&#xD;
         20. Any use of medication&#xD;
&#xD;
               1. strong or moderate clinical CYP 3A/3A4 inhibitors or inducers within 30 days&#xD;
&#xD;
               2. prescription medication within 14 days&#xD;
&#xD;
               3. over-the-counter products and natural health products within 7 days&#xD;
&#xD;
               4. prescription medication known to affect platelet function within 14 days&#xD;
&#xD;
               5. a depot injection or an implant of any drug within 3 months&#xD;
&#xD;
               6. use of IA corticosteroid, hyaluronic acid, or other IA injection in the study&#xD;
                  knee within 6 months&#xD;
&#xD;
               7. any IA injection drug that could impact endogenous steroid levels within 6 months&#xD;
&#xD;
               8. systemic corticosteroids within 30 days&#xD;
&#xD;
               9. use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory&#xD;
                  diseases within 6 months&#xD;
&#xD;
         21. Donation of plasma within 7 days. Donation or loss of blood of 50mL to 499 mL of blood&#xD;
             within 30 days, or more than 499 mL within 56 days&#xD;
&#xD;
         22. Female subjects who are pregnant, breast-feeding, or plan to become&#xD;
             pregnant/breast-feeding&#xD;
&#xD;
         23. History of latent or active tuberculosis or exposure to endemic areas within 8 weeks&#xD;
&#xD;
         24. Positive TB test indicating possible tuberculosis infection&#xD;
&#xD;
         25. Immunization with a live attenuated vaccine 1 month or planned during the course of&#xD;
             the study&#xD;
&#xD;
         26. History of clinically significant opportunistic infection&#xD;
&#xD;
         27. Serious local infection or systemic infection within the 3 months&#xD;
&#xD;
         28. Presence of a symptomatic viral or bacterial infection within 2 weeks&#xD;
&#xD;
         29. Subjects with current diagnosis of severe OA with grade 4 classification in the&#xD;
             non-study knee based on the Kellgren-Lawrence grades&#xD;
&#xD;
         30. Subject who had a surgery within 4 weeks or expected to have knee replacement surgery&#xD;
             scheduled during his/her study duration&#xD;
&#xD;
         31. Subjects with known history of adrenal insufficiency or with potential risk of adrenal&#xD;
             insufficiency&#xD;
&#xD;
         32. History of allergic reactions to cosyntropin&#xD;
&#xD;
         33. Patient with any lower limb amputation&#xD;
&#xD;
         34. Unwilling to undergo synovial fluid collection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carl Brown, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Taiwan Liposome Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Research Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Panax Clinical Research</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Coast Research Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Syneos Health</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Futuro Clinical Trials, LLC.</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JBR Clinical Research</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tri-Service General Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Municipal Wanfang Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>116</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>July 6, 2022</last_update_submitted>
  <last_update_submitted_qc>July 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Dexamethasone 21-phosphate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03754049
org study id: TLC599A2004
nct id: NCT03754049
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is a Phase 2, open-label, 1-period, parallel study with 9 cohorts of subjects with
      OA of the knee enrolled to receive single-dose of TLC599 or DSP via IA injection.
This Phase 2, open-label, 1 period, parallel study will enroll approximately 90 subjects to
      receive a single dose of TLC599 or DSP via IA injection, followed by a PK evaluation period
      up to 24 weeks and an additional follow-up period of 1 to 5 weeks. Additional subjects may be
      recruited as needed to achieve at least 10 subjects completing the 1-week blood collection
      period for each treatment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the Curve [AUC]
time frame: Baseline till 24 weeks post IP administration
description: Area under the concentration-time curve
measure: Cmax: maximum concentration
time frame: Baseline till 24 weeks post IP administration
description: Maximum concentration
measure: Tmax: time to peak concentration
time frame: Baseline till 24 weeks post IP administration
description: Time to peak concentration
measure: Number of AEs, including SAE and treatment-emergent AE
time frame: Screening till 25 weeks post IP administration
description: Number of AEs, including SAE and treatment-emergent AE
measure: Cortisol concentration
time frame: baseline till 24 weeks post IP administration
description: Cortisol concentration
arm group label: TLC599 12 mg
arm group type: Experimental
description: 12 mg DSP with 100 μmol phospholipid via IA injection;
arm group label: TLC599 6 mg
arm group type: Experimental
description: 6 mg DSP with 50 μmol phospholipid via IA injection.
arm group label: DSP 4mg
arm group type: Active Comparator
description: Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA injection.
intervention type: Drug
intervention name: TLC599
description: TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
arm group label: TLC599 12 mg
arm group label: TLC599 6 mg
other name: TLC599 Injection
intervention type: Drug
intervention name: DSP
description: Dexamethasone sodium phosphate (DSP) is a glucocorticoid widely used in the treatment of joint pain such as gout, osteoarthritis and rheumatoid arthritis via IA injection.
arm group label: DSP 4mg
other name: Dexamethasone Sodium Phosphate
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Carl Brown, PhD
role: Study Director
affiliation: Taiwan Liposome Company
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Dexamethasone 21-phosphate
mesh term: BB 1101
sharing ipd: No