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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 : Not yet recruiting
First Posted : November 27, 2018
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Taiwan Liposome Company

Brief Summary:
This study is a single-center, Phase 2, open-label, 1-period, parallel study with 8 cohorts of subjects with OA of the knee sequentially enrolled to receive single-dose of TLC599 or DSP via IA injection.

Condition or disease Intervention/treatment Phase
OSTEOARTHRITIS OF THE KNEE Drug: TLC599 Drug: DSP Phase 2

Detailed Description:
This single center, Phase 2, open-label, 1 period, parallel study will sequentially enroll approximately 80 subjects in 8 cohorts to receive a single dose of TLC599 or DSP via IA injection, followed by a PK evaluation period up to 20 weeks and an additional follow-up period of 1 to 5 weeks. Additional subjects will be recruited to the assigned cohorts as needed, to achieve at least 6 subjects per cohort with adequate SF volume for DP and DEX concentration analysis at EOPK.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 9, 2019
Estimated Primary Completion Date : January 9, 2020
Estimated Study Completion Date : January 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: TLC599 12 mg
12 mg DSP with 100 μmol phospholipid (1.0 mL) via IA injection;
Drug: TLC599
TLC599 (TLC599 Injection) is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
Other Name: TLC599 Injection

Experimental: TLC599 6 mg
6 mg DSP with 50 μmol phospholipid (0.5 mL) via IA injection.
Drug: TLC599
TLC599 (TLC599 Injection) is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
Other Name: TLC599 Injection

Active Comparator: DSP 4mg
Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA 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. DSP is the pro-drug of the corticosteroid dexamethasone (DEX), which is a highly potent glucocorticoid whose action is mediated by the binding of the corticosteroid molecule to receptor located within sensitive cells.
Other Name: Dexamethasone Sodium Phosphate




Primary Outcome Measures :
  1. Area under the Curve [AUC] [ Time Frame: Baseline till 20 weeks post IP administration ]
    Area under the concentration-time curve

  2. Cmax: maximum concentration [ Time Frame: Baseline till 20 weeks post IP administration ]
    Maximum concentration

  3. Tmax: time to peak concentration [ Time Frame: Baseline till 20 weeks post IP administration ]
    Time to peak concentration


Secondary Outcome Measures :
  1. 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

  2. Cortisol concentration [ Time Frame: baseline till 1, 6, 12, 16, 20 weeks post IP administration ]
    Cortisol concentration



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects, non-smokers or moderate smokers, 50 years or older, with BMI ≤ 40.0 kg/m2.
  2. Has any symptoms associated with OA of the knee for at least 6 months prior to the Screening Visit 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 must be willing to use acceptable contraceptive methods for 21 weeks after study drug administration.
  5. Male subjects must be willing 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. Any 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. Any 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 Visit.
  10. Total white blood cell count <3000/ μL or >13000/ μL.
  11. History of acquired or congenital immunodeficiency diseases.
  12. A history of treated malignancy which is disease free for ≤ 5 years prior to the Screening Visit, 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 Visit.
  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 Visit or regular use of alcohol within six months prior to the Screening Visit.
  17. History of significant drug abuse within one year prior to the Screening Visitor use of soft drugs within 3 months prior to the Screening Visit or hard drugs within 1 year prior to the Screening Visit.
  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. any 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. any 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 Visit.
  23. Positive QuantiFERON®-TB test indicating possible tuberculosis infection at the Screening Visit.
  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 Visit.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03754049


Contacts
Contact: Cheng-Yu Kuo +886 2 2655 7377 ext 202 chengyu@tlcbio.com

Locations
United States, Florida
Syneos Health Not yet recruiting
Miami, Florida, United States, 33136
Sponsors and Collaborators
Taiwan Liposome Company
Investigators
Study Director: Carl Brown, PhD Taiwan Liposome Company

Responsible Party: Taiwan Liposome Company
ClinicalTrials.gov Identifier: NCT03754049     History of Changes
Other Study ID Numbers: TLC599A2004
First Posted: November 27, 2018    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action