A Phase 2, Open Label, Pharmacokinetic (PK) Study of TLC599 in Subjects With Osteoarthritis of the Knee

A Phase 2, Open-label, Pharmacokinetic (PK) Study of a Single Intra-articular Administration of TLC599 in Subjects With Mild to Moderate Osteoarthritis of the Knee

This study is a multi-center, Phase 2, open-label, 1-period, parallel study with 9 cohorts of subjects with osteoarthritis (OA) of the knee enrolled to receive single-dose of TLC599 or Dexamethasone sodium phosphate (DSP) via IA injection and 1 cohort of healthy subjects to receive single-dose of DSP via intravenous (IV) injection.

This Phase 2, open-label, 1 period, parallel study will enroll

1. approximately 90 subjects to receive a single dose of TLC599 or DSP via intra-articular (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.
2. approximately 12 healthy subjects to receive a single dose of DSP via IV injection, followed by a PK evaluation period up to 1 week and an additional follow-up period of 1 week. Additional subjects may be recruited as needed to achieve at least 12 subjects completing the 48-hour blood collection period for IV DSP.

Study Criteria for Patients with OA of the Knee (Cohort G1-G9)

Inclusion Criteria:

• Age 45 or older, non or moderate smokers, body mass index (BMI) ≤ 40.0 kg/m2.
• Knee OA symptoms with confirmed mild to moderate OA.
• Study knee OA severity grade 1-3 (Kellgren-Lawrence).
• Agree to use contraception

Exclusion Criteria:

• Clinically significant (CS) abnormalities (physical, lab, hepatitis B/C, HIV, electrocardiogram [ECG], vital sign or unstable illness).
• Positive urine drug screen, tuberculosis (TB) test; significant alcohol/drug abuse
• Allergic reactions to TLC599, its components, related drugs or cosyntropin.
• History of autoimmune disease, immunodeficiency diseases, treated malignancy, CS opportunistic infection, tuberculosis, infective arthritis or concurrent knee infection
• Intra-articular bleeding in study knee.
• Skin issues at injection site or hindrance to knee joint penetration.
• Blood coagulation disorders.
• Stroke or myocardial infarction
• Poorly controlled hypertension or vital sign abnormalities.
• Interfering conditions with dosing, visits, or compliance or refusal of synovial fluid collection.
• Medication: Strong/moderate Cytochrome P450 (CYP) 3A/3A4 inhibitors/inducers, prescription meds, over-the-counter (OTC)/natural health products, meds affecting platelet function, depot injection/implant, IA corticosteroid, hyaluronic acid, or other injection in study knee, impact on endogenous steroid levels, systemic corticosteroids, live attenuated vaccine, chemotherapeutic/immunosuppressant use for inflammatory diseases.
• Plasma donation or significant blood loss.
• Pregnancy, breastfeeding, or planning to be pregnant/breastfeed
• Serious local/systemic infection or symptomatic viral/bacterial infection
• Severe OA (grade 4) in non-study knee (Kellgren-Lawrence).
• Recent surgery, scheduled knee replacement or lower limb amputation.
• Known/adrenal insufficiency risk.
• Recent participation in other study research

Study Criteria for Healthy Subjects (Cohort G10)

Inclusion Criteria:

• Age 18-45, non-smokers, BMI 18.5-25 kg/m2, body weight ≥ 50.0 kg (males) or ≥ 45.0 kg (females).
• Healthy with no CS illness/surgery within 4 weeks or CS medical history.
• Agree to use contraception
• No new tattoos/body piercings at the injection site until the study ends.

Exclusion Criteria:

• CS abnormal physical, ECG or vital sign findings.
• Known/adrenal insufficiency risk.
• Abnormal lab results (HBV, HCV, HIV, TB).
• Positive pregnancy test or lactating; positive urine drug screen or cotinine test.
• Significant alcohol/drug abuse or positive alcohol test.
• Significant drug allergies or allergic reactions to DSP, dexamethasone, cosyntropin, natural adrenocorticotropic hormone (ACTH), or other related drugs.
• History/presence of conditions including CS opportunistic infection, serious local/systemic infection, autoimmune, blood, heart, vascular, respiratory, lung, skin, liver, gallbladder, retinopathy, neuromuscular, cancer, kidney, diabetes, severe allergic reactions, or others that would preclude participation.
• Fever
• Active/latent tuberculosis or symptomatic viral/bacterial infection
• Medication: Depot injection/implant, vaccine, drug known to induce or inhibit CYP3A4 metabolism, prescription meds, OTC/natural health products.
• Consumption of specified fruits.
• Recent participation in other study research
• Plasma donation or significant blood loss.
• Reasons preventing study participation