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

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.

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)