Osteoarthritis of the Knee
Conditions
Brief 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.
Detailed description
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.
Interventions
DRUGTLC599
TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
DRUGDSP
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.
Sponsors
Taiwan Liposome Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the Curve [AUC] | Baseline till 24 weeks post investigational product (IP) administration | Area under the concentration-time curve |
| Cmax: maximum concentration | Baseline till 24 weeks post IP administration | Maximum concentration |
| Tmax: time to peak concentration | Baseline till 24 weeks post IP administration | Time to peak concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events (AEs), including serious adverse event (SAE) and treatment-emergent AE | Screening till 25 weeks post IP administration | Number of AEs, including SAE and treatment-emergent AE |
| Cortisol concentration | baseline till 24 weeks post IP administration | Cortisol concentration |
Countries
Taiwan, United States
Outcome results
None listed