Extended and Controlled Release Liposomal Formulated Dexamethasone for Chronic Knee OA Pain

Study Overview
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Brief Summary
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Phase 3 randomized, double-blind, placebo- and active comparator-controlled study of TLC599.

Detailed Description
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This is a Phase 3 randomized, double-blind, placebo- and active comparator-controlled pivotal study. Approximately 500 adult patients with moderate to severe pain due to OA of the knee will be enrolled and randomized. All patients will be followed for a total of 52 weeks. Efficacy and safety of 2 doses of TLC599 will be evaluated in comparison to Placebo and DSP through Week 52.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo- and Active-controlled Study to Evaluate the Efficacy and Safety of TLC599 in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: TLC599
* Drug: DSP
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥40 years of age. BMI ≤ 40 kg/m2. Radiographically documented OA with Kellgren-Lawrence severity Grade 2 or 3 and associated symptoms Patient-reported pain with NRS score ≥4 (on a 0-10 scale) Able to read, understand, and sign the informed consent form, communicate with the investigator, complete study diaries, and understand and comply with protocol requirements. Exclusion Criteria: Recent use of IA or systemic corticosteroids Patient who is not ambulatory Any surgery or arthroscopy in the index knee within 12 months Any condition that could possibly confound the patient's assessment of index knee pain Substance abuse disorder, or positive urine drug test for illegal drug substances History of acquired or congenital immunodeficiency diseases History of treated malignancy which is disease free for ≤5 years Known allergy or hypersensitivity to the study drugs or their components

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLC599<br>TLC599 (1mL) IA injection | Drug: TLC599<br>* TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient)<br>* Other names: TLC599 Injection;|
| Active Comparator: Dexamethasone sodium phosphate<br>DSP 4mg (1mL) IA injection | Drug: TLC599<br>* TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient)<br>* Other names: TLC599 Injection;Drug: DSP<br>* 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.<br>* Other names: Dexamethasone Sodium Phosphate;|
| Placebo Comparator: Normal Saline<br>Normal saline (1mL) IA injection | Other: Normal Saline<br>* 0.9% normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in WOMAC Pain | Change from Baseline in WOMAC Pain | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in WOMAC Pain | Change from Baseline in WOMAC Pain | Baseline, Week 16 | 
| Change from Baseline in WOMAC Pain | Change from Baseline in WOMAC Pain | Baseline, Week 20 | 
| Change from Baseline in WOMAC Pain | Change from Baseline in WOMAC Pain | Baseline, Week 24 | 
| Change from Baseline in WOMAC Pain | Change from Baseline in WOMAC Pain | Baseline, Week 36 | 
| Change from Baseline in WOMAC Function at Week 12 (Group A vs. Group C) | Change from Baseline in WOMAC Function at Week 12 (Group A vs. Group C) | Baseline, Week 12 | 
| PGIC | Patient Global Impression of Change | Week 12 | 
| Total rescue acetaminophen consumption | Total rescue acetaminophen consumption | through Week 12 | 
| Durable responder with ≥30% decrease in WOMAC Pain from Baseline | Durable responder with ≥30% decrease in WOMAC Pain from Baseline | Weeks 4 through 12 | 
| Change from Baseline in WOMAC Function | Change from Baseline in WOMAC Function | Baseline, Week 36 | 
| PGIC | Patient Global Impression of Change | Week 36 | 
| Change from Baseline in WOMAC Pain at Week 12 (Group A vs. Group B) | Change from Baseline in WOMAC Pain at Week 12 (Group A vs. Group B) | Baseline, Week 12 | 
| Change from Baseline in WOMAC Pain at Week 52 (Group A vs. Group C) | Change from Baseline in WOMAC Pain at Week 52 (Group A vs. Group C) | Baseline, Week 52 |