Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for TLC599 in OA Patients

Study Overview
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Brief Summary
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This trial is a Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study to investigate the safety and efficacy of TLC599 in subjects with osteoarthritis of the knee.

Detailed Description
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Protocol No: TLC599A2003 Name of Finished Product: TLC599 Title of Study: A Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study for Single dose Administration of TLC599 in Patients with Osteoarthritis (OA) of Knee. Study duration: The trial will last around 27 weeks including a 21-day screening period and a 24-week follow-up period.

Official Title
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A Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for Single Dose Administration of TLC599 in Patients With Osteoarthritis (OA) of Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: TLC599 LD group
* Drug: Normal Saline
* Drug: TLC599 HD group


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male or female patients, at least 50 years of age. Documented diagnosis of OA of the knee for at least 6 months The study knee has OA with Grade 2 to 3 severity based on the Kellgren Lawrence grades Patients with patient related visual analogue scale (VAS) score of 5.0 to 9.0 at baseline. Willing and able to comply with study procedures and provide written informed consent. Main Exclusion Criteria: Patients who received systemic corticosteroids within the last 30 days prior to dosing. Patients who use prohibited medications within 7 days prior to study drug administration or any pain control medication including acetaminophen within 48 hours prior to study drug administration. Patients who use prohibited medications other than acetaminophen and oral NSAIDs from screening visit to 7 days prior to study drug administration. Documented history and confirmed autoimmune disease History of post-traumatic knee arthritis, or evidence of intra articular bleeding of the study knee History of infective arthritis Unstable study knee joint Use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee within 3 months prior to the screening visit. A history of treated malignancy which is disease free for ≤ 5 years prior to the screening visit Uncontrolled and unstable concurrent medical or psychiatric illness, that will jeopardize the safety of the patient Use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months prior to the screening visit. Current use of anticoagulants, including warfarin, heparin, low molecular weight heparin, or dabigatran. Abnormalities of laboratory parameters as described below will qualify for exclusion: hemoglobin < 8 g/dL; total white blood cell count < 4000/ µL; serum bilirubin/ alanine aminotransferase/ aspartate aminotransferase > 2 times upper limit of normal (ULN) for the laboratory reference ranges; serum creatinine > 2 times ULN for the laboratory reference range; serum uric acid > ULN for the laboratory reference range; prothrombin time/International Normalized Ratio > ULN for the laboratory reference range. Contraindication to undergoing magnetic resonance imaging (MRI)

Ages Eligible for Study
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Minimum Age: 50 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLC599 LD group<br>12 mg DSP with 100 µmol PL (1.0 mL) | Drug: TLC599 LD group<br>* Single dose via intra-articular injection<br>* Other names: 12 mg DSP with 100 µmol PL (1.0 mL);|
| Experimental: TLC599 HD group<br>18 mg DSP with 150 µmol PL (1.5 mL) | Drug: TLC599 HD group<br>* Single dose via intra-articular injection<br>* Other names: 18 mg DSP with 150 µmol PL (1.5 mL);|
| Placebo Comparator: Placebo group<br>1.5 mL normal saline | Drug: Normal Saline<br>* Single dose via intra-articular injection<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC questionnaire pain sub-scale | The primary endpoint is to evaluate the change from baseline by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale through Week 12. | from dosing through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC questionnaire pain sub-scale | Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in pain / function subscales of WOMAC. | at Weeks 1, 4, 8, 12, 16, 20, and 24 | 
| Pain score (VAS) | Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS). | at Weeks 1, 4, 8, 12, 16, 20, and 24 | 
| Pain score (VAS) | Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS). | from dosing through Week 12, 16, 20, 24 | 
| WOMAC questionnaire pain sub-scale | Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS). | from dosing through Week 12, 16, 20, 24 | 
| EuroQol-5 Dimension questionnaire | Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in EuroQol-5 Dimension questionnaire. | at Weeks 1, 4, 8, 12, 16, 20, and 24 | 
| Usage of acetaminophen | Total consumption of acetaminophen at Weeks 1, 4, 8, 12, 16, 20, and 24. | at Weeks 1, 4, 8, 12, 16, 20, and 24 | 
| Incidence of Treatment-Emergent Adverse Events | To evaluate the safety and tolerability of TLC599 by incidence of Treatment-Emergent Adverse Events reported by Investigators | up to 24 weeks after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis of the knee, TLC599, Dexamethasone, DSP