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

TLC599A2004

This study is a multi-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 and 1 cohort of healthy subjects to receive single-dose of DSP via IV injection.

2019-01-21

2023-11-07

2023-11-07

Completed

Early phase I

102

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 102, 'type': 'ACTUAL'}}

2024-01-08