Clinical Trial Finder

Cohort G1-G9 Study Criteria.

Inclusion Criteria:

• - Age 45 or older, non or moderate smokers, 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:

• - CS abnormalities (physical, lab, hepatitis B/C, HIV, ECG, vital sign or unstable illness).

• - Positive urine drug screen, 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 CYP 3A/3A4 inhibitors/inducers, prescription meds, 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.

Cohort G10 (Healthy Subjects) Study Criteria.

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 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

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 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 recieve 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.

Arms

Experimental: TLC599 12 mg

12 mg DSP with 100 μmol phospholipid via IA injection;

Experimental: TLC599 6 mg

6 mg DSP with 50 μmol phospholipid via IA injection.

Active Comparator: DSP 4mg

Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA injection.

Active Comparator: DSP 10mg

Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 2.5 mL via IV injection.

Interventions

Drug: - TLC599

TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).

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.