a phase 2, open label, pharmacokinetic (pk) study of tlc599 in subjects with osteoarthritis of the knee

Conditions: Osteoarthritis of the Knee

Summary: 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.

Eligibility criteria:
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