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

This is an interventional treatment trial for OSTEOARTHRITIS OF THE KNEE Read More

Inclusion Criteria:

1. Male or female non or moderate smokers, 45 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 until 25 weeks after study drug administration
5. Male subjects must to use acceptable contraceptive methods from dosing until 25 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, laboratory test results or positive test for hepatitis B, hepatitis C, or HIV
2. Positive urine drug screen
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
7. History of infective arthritis or suspected / concurrent infection in the study knee; clinical symptoms and signs of acute infection or infection-related inflammation in the non-study knee
8. Skin lesion/breakdown at the anticipated injection site or any condition that would impair penetration of the study knee joint space.
9. Blood coagulation disorders
10. Total white blood cell count <4000/ μL or >13000/ μL
11. History of acquired or congenital immunodeficiency diseases
12. History of treated malignancy which is disease free for ≤ 5 years
13. Stroke or myocardial infarction within 3 months
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
16. Poorly controlled hypertension or vital sign abnormalities
17. History of significant alcohol abuse within one year or regular use of alcohol within six months
18. History of significant drug abuse within one year or use of soft drugs within 3 months or hard drugs within 1 year
19. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days, administration of a biological product in the context of a clinical research study within 90 days

20. Any use of medication

    1. strong or moderate clinical CYP 3A/3A4 inhibitors or inducers within 30 days
    2. prescription medication within 14 days
    3. over-the-counter products and natural health products within 7 days
    4. prescription medication known to affect platelet function within 14 days
    5. a depot injection or an implant of any drug within 3 months
    6. use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee within 6 months
    7. any IA injection drug that could impact endogenous steroid levels within 6 months
    8. systemic corticosteroids within 30 days
    9. use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months
21. Donation of plasma within 7 days. Donation or loss of blood of 50mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days
22. Female subjects who are pregnant, breast-feeding, or plan to become pregnant/breast-feeding
23. History of latent or active tuberculosis or exposure to endemic areas within 8 weeks
24. Positive TB test indicating possible tuberculosis infection
25. Immunization with a live attenuated vaccine 1 month or planned during the course of the study
26. History of clinically significant opportunistic infection
27. Serious local infection or systemic infection within the 3 months
28. Presence of a symptomatic viral or bacterial infection within 2 weeks
29. Subjects with current diagnosis of severe OA with grade 4 classification in the non-study knee based on the Kellgren-Lawrence grades
30. Subject who had a surgery within 4 weeks or expected to have knee replacement surgery scheduled during his/her study duration
31. Subjects with known history of adrenal insufficiency or with potential risk of adrenal insufficiency
32. History of allergic reactions to cosyntropin
33. Patient with any lower limb amputation
34. Unwilling to undergo synovial fluid collection