Study of Intra-articular Injections vs Placebo in Patients With Pain From Osteoarthritis of the Knee

Inclusion Criteria (Screening Visit 1):

• Osteoarthritis (OA) of the knee by American College of Rheumatology criteria
• Men or women between 45-80 years of age.
• Have documented diagnosis of primary OA of the target knee based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment of the target knee confirmed by standard post-anterior weightbearing X-ray of the knee in full extension taken 38 kg/m2.
• Avoidance of, or aversion to, nonprescription medications.
• Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy
• Any major injury or surgery to the target knee in the prior 12 months.
• One or a combination of the following co-morbidities:
• other inflammatory arthropathies, gout or pseudogout within previous 6 months
• avascular necrosis
• severe bone or joint deformity in target knee
• osteonecrosis of either knee
• fibromyalgia
• pes anserine bursitis
• lumbar radiculopathy with referred pain to either knee
• neurogenic or vascular claudication
• significant anterior knee pain due to diagnosed isolated patella-femoral syndrome in the target knee
• target knee joint infection or skin disorder/infection to the area surrounding the knee within previous 6 months
• current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)
• Participated in any experimental drug or device study within the prior one (1) month and/or IA injections six (6) months.
• Referred pain from other joints
• Significantly debilitating concurrent infection(s)
• Significant ligamentous instability
• Any prior viscosupplementation therapy (in target knee) within 6 months prior to Screening
• Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment
• Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products containing glucosamine and/or chondroitin sulphate and/or diacerein
• Therapy with opioids within the last 90 days including intra-dermal delivery systems (patches)
• Therapy with autologous stem cells
• Therapy with coumarins such as warfarin, Coumadin; heparin and derivative substances including low molecular weight heparin, synthetic pentasaccharide inhibitors of factor Xa such as fondaparinux and idraparinux; direct factor Xa inhibitors such as rivaroxaban and apixaban; direct thrombin inhibitors such as hirudin, lepirudin, bivalirudin, argatroban and dabigatran.
• Concomitant inflammatory or other rheumatologic, neurological or cardiovascular diseases which could affect the evaluation of knee pain
• Ongoing litigation for workers compensation for musculoskeletal injuries or disorders
• Use of alcohol of more than 4 drinks per day
• Clinically important axial deviation (varus, valgus) greater than 15 degrees
• Concomitant severe OA of the hip or other joints, which might interfere with the assessments required by the study
• Painful knee conditions other than OA (e.g., Paget's disease)
• Hemiparesis of lower limbs
• Significant planned surgery to lower limbs, which might interfere with the patient's ability to comply with study requirements
• Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular, neurological disease that might interfere with the outcome of the study or the patient's ability to comply with study requirements
• Presence of infections and/or skin diseases in the area of the injection site such as psoriasis
• Females who are pregnant or breast-feeding or not using recognized effective contraceptive measures. Females of childbearing potential (including those less than one year post-menopausal) must agree to maintain reliable birth control throughout the study.
• Clinically significant abnormal laboratory values.
• Patients who are likely to be non-compliant or uncooperative during the study.