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A Phase 2, Open Label, PK Study of TLC599 in Subject With Osteoarthritis of the Knee

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ClinicalTrials.gov Identifier: NCT03754049
Recruitment Status : Recruiting
First Posted : November 27, 2018
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Taiwan Liposome Company

Tracking Information
First Submitted Date  ICMJE November 16, 2018
First Posted Date  ICMJE November 27, 2018
Last Update Posted Date February 26, 2019
Actual Study Start Date  ICMJE January 21, 2019
Estimated Primary Completion Date January 9, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2019)
  • Area under the Curve [AUC] [ Time Frame: Baseline till 24 weeks post IP administration ]
    Area under the concentration-time curve
  • Cmax: maximum concentration [ Time Frame: Baseline till 24 weeks post IP administration ]
    Maximum concentration
  • Tmax: time to peak concentration [ Time Frame: Baseline till 24 weeks post IP administration ]
    Time to peak concentration
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2018)
  • Area under the Curve [AUC] [ Time Frame: Baseline till 20 weeks post IP administration ]
    Area under the concentration-time curve
  • Cmax: maximum concentration [ Time Frame: Baseline till 20 weeks post IP administration ]
    Maximum concentration
  • Tmax: time to peak concentration [ Time Frame: Baseline till 20 weeks post IP administration ]
    Time to peak concentration
Change History Complete list of historical versions of study NCT03754049 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2019)
  • Number of AEs, including SAE and treatment-emergent AE [ Time Frame: Screening till 25 weeks post IP administration ]
    Number of AEs, including SAE and treatment-emergent AE
  • Cortisol concentration [ Time Frame: baseline till 24 weeks post IP administration ]
    Cortisol concentration
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2018)
  • Number of SAEs and treatment-related severe AEs [ Time Frame: Screening till 6, 7, 13, 17, and 21 weeks post IP administration ]
    Number of SAEs and treatment-related severe AEs
  • Cortisol concentration [ Time Frame: baseline till 1, 6, 12, 16, 20 weeks post IP administration ]
    Cortisol concentration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2, Open Label, PK Study of TLC599 in Subject With Osteoarthritis of the Knee
Official Title  ICMJE 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
Brief Summary This study is a single-center, 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.
Detailed Description This single center, 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 will be recruited as needed, to achieve at least 6 subjects per cohort with adequate SF volume for DP and DEX concentration analysis at EOPK.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE OSTEOARTHRITIS OF THE KNEE
Intervention  ICMJE
  • Drug: TLC599
    TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
    Other Name: TLC599 Injection
  • Drug: DSP
    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.
    Other Name: Dexamethasone Sodium Phosphate
Study Arms  ICMJE
  • Experimental: TLC599 12 mg
    12 mg DSP with 100 μmol phospholipid via IA injection;
    Intervention: Drug: TLC599
  • Experimental: TLC599 6 mg
    6 mg DSP with 50 μmol phospholipid via IA injection.
    Intervention: Drug: TLC599
  • Active Comparator: DSP 4mg
    Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA injection.
    Intervention: Drug: DSP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 23, 2019)
90
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2018)
80
Estimated Study Completion Date  ICMJE January 16, 2020
Estimated Primary Completion Date January 9, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female non or moderate smokers, 50 years or older, with BMI ≤ 40.0 kg/m2.
  2. Has symptoms associated with OA of the knee for at least 6 months prior to Screening and confirmation of mild to moderate OA.
  3. The study knee has OA with grade 1-3 in severity based on the Kellgren-Lawrence grades.
  4. Females of childbearing potential to use acceptable contraceptive methods for 21 weeks after study drug administration.
  5. Male subjects must to use acceptable contraceptive methods from dosing until 21 weeks after study drug administration.
  6. Willing and able to comply with study procedures and provide written informed consent.

Exclusion Criteria:

  1. Clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for hepatitis B, hepatitis C, or HIV found during screening.
  2. Positive urine drug screen at screening.
  3. History of allergic reactions to TLC599, its components or other related drugs.
  4. Clinically significant and unstable illness.
  5. History of clinically significant autoimmune disease.
  6. Evidence of intra articular bleeding of the study knee at baseline prior to study drug administration.
  7. History of infective arthritis or suspected / concurrent infection in the study knee at baseline prior to study drug administration; clinical symptoms and signs of acute infection or infection-related inflammation in the non-study knee before study drug administration.
  8. Skin lesion/breakdown at the anticipated injection site or any condition that would impair penetration of the study knee joint space.
  9. Platelet count < 80,000/μL, or blood coagulation disorders at the Screening.
  10. Total white blood cell count <3000/ μL or >13000/ μL.
  11. History of acquired or congenital immunodeficiency diseases.
  12. History of treated malignancy which is disease free for ≤ 5 years prior to the Screening, except for basal cell carcinoma and squamous cell carcinoma of skin or carcinoma in situ of the uterine cervix.
  13. Stroke or myocardial infarction within 3 months prior to the Screening.
  14. Subjects with a condition or in a situation which will interfere with the subject's ability to comply or cooperate with the dosing and visit schedules and the protocol evaluations or may not be suitable for this study.
  15. Clinically significant ECG abnormalities or vital sign abnormalities at screening.
  16. History of significant alcohol abuse within one year prior to the Screening or regular use of alcohol within six months prior to the Screening.
  17. History of significant drug abuse within one year prior to the Screening or use of soft drugs within 3 months prior to the Screening or hard drugs within 1 year prior to the Screening.
  18. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing, administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration.
  19. Any use of medication;

    1. drugs known to induce or inhibit hepatic CYP 3A4 metabolism within 30 days prior to dosing;
    2. prescription medication within 14 days prior to dosing;
    3. over-the-counter products and natural health products within 7 days prior to dosing;
    4. prescription medication known to affect platelet function within 14 days prior to dosing;
    5. a depot injection or an implant of any drug within 3 months prior to dosing;
    6. use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee within 4 months prior to dosing;
    7. any IA injection drug that could impact endogenous steroid levels within 6 months prior to dosing;
    8. systemic corticosteroids within 30 days prior to dosing;
    9. use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months prior to dosing.
  20. Donation of plasma within 7 days prior to dosing. Donation or loss of blood of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing.
  21. Female subjects who are pregnant, breast-feeding, or plan to become pregnant/breast-feeding.
  22. History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to the Screening.
  23. Positive QuantiFERON®-TB test indicating possible tuberculosis infection at the Screening.
  24. Immunization with a live attenuated vaccine 1 month prior to dosing or planned vaccination during the course of the study.
  25. History of clinically significant opportunistic infection.
  26. Serious local infection or systemic infection within the 3 months prior to the Screening.
  27. Presence of fever associated with a symptomatic viral or bacterial infection within 2 weeks prior to dosing.
  28. Subjects with previous diagnosis of severe OA with grade 4 classification based on the Kellgren-Lawrence grades.
  29. Subject who had a surgery within 4 weeks prior to dosing or expected to have a knee replacement surgery scheduled within 21 weeks after the study drug administration.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cheng-Yu Kuo +886 2 2655 7377 ext 202 chengyu@tlcbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03754049
Other Study ID Numbers  ICMJE TLC599A2004
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Taiwan Liposome Company
Study Sponsor  ICMJE Taiwan Liposome Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Carl Brown, PhD Taiwan Liposome Company
PRS Account Taiwan Liposome Company
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP