Investigation of 1.2% Sodium Hyaluronate for Treatment of Painful Chronic Osteoarthritis of the Knee

A 26 Week, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Single Intra-Articular Injection 1.2% Sodium Hyaluronate for Treatment of Painful Osteoarthritis of the Knee, With Optional 26-Week Open-Label Safety Extension

Subjects with chronic osteoarthritis of the knee will be assigned to receive an injection of either 1.2% sodium hyaluronate or buffered saline to evaluate its effectiveness and safety for 26 weeks. After 26 weeks, subjects can elect to receive a second injection of 1.2% sodium hyaluronate and be followed for another 26 weeks.

Inclusion Criteria:

• Chronic osteoarthritis (OA) of target knee confirmed by American College of Rheumatology (ACR) Criteria.
• Pain due to OA in target knee present for at least 6 months.
• During Screening and Baseline visits, subjects will require a visual analog scale (VAS) score (100 mm) of ≥ 41 mm and ≤ 90 mm, recorded immediately following a 50-foot walk, AND at Baseline, cannot have decreased >10mm (improvement) from Screening.
• A bilateral standing anteroposterior (AP) X-ray confirming OA of the target knee.
• Ability and willingness to use only acetaminophen as the analgesic (rescue) study medication
• Ability to perform procedures required of the pain index evaluations (unassisted walking 50 feet on a flat surface and going up and down stairs).
• Willingness and ability to complete efficacy and safety questionnaires and ability to read and understand study instructions.
• Signed Subject Informed Consent Form

Exclusion Criteria:

• Any major injury (including sports injuries) to the target knee within the prior 12 months.
• Any surgery to the target knee, hip and contralateral hip within the prior 12 months.
• Major and minor articular procedures
• Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis.
• Gout or calcium pyrophosphate (pseudogout) diseases of the target knee that have flared within the previous 6 months.
• X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee.
• Osteonecrosis of either knee.
• Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication.
• Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee.
• Significant target knee joint infection or skin disorder/infection within the previous 6 months prior to study enrollment.
• Symptomatic OA of the hips, spine, or ankle, if it would interfere with the evaluation of the target knee.
• Known hypersensitivity to acetaminophen, sodium hyaluronate, or phosphate buffered saline solution.
• Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the entire study period.
• Recurrent medical history of severe allergic or immune-mediated reactions or other immune disorders.
• Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation.
• Current treatment or treatment within the previous 2 years prior to Screening for any malignancy unless specific written permission is provided by the Sponsor (excluding basal cell or squamous cell carcinoma of the skin).
• Chronic liver disease and active liver disease based on liver profile of aspartate aminotransferase (AST), alanine transaminase (ALT), and conjugated bilirubin >2 times the upper limit of normal.
• Renal insufficiency based on serum creatinine >2.0 mg/dL.
• Any clinically significant laboratory value based on clinical history that the Investigator feels may affect the study evaluation.
• Any intercurrent chronic disease or condition that may interfere with the completion of the 6-month (or 12-month) follow-up of the study, such as liver disease, severe coronary disease, drug abuse, disordered mental state, or other clinically significant condition.
• Current alcoholism, and/or any known current addiction to pain medications.
• Any clinically significant finding that would place the patient at health risk, impact the study, or affect the completion of the study.
• Any psychiatric illness that would prevent comprehension of the details and nature of the study.
• Participation in any experimental device study within 6 months prior to the Screening, or an experimental drug study within 1 month prior to the Screening