Inclusion Criteria:  Aged between 40 and 80 years (inclusive, ≥ 40 and ≤ 80 years); Symptomatic knee osteoarthritis as defined by the American College of Rheumatology (ACR) criteria (for subjects with OA at both knees, the most painful one will be included in the study only, respecting Kellgren-Lowrance grade II or III); Ambulant without assistance; Kellgren-Lawrence grade II or III on X-ray performed at maximum 6 months before screening; Visual Analogue Scale (VAS) score knee pain ≥40 at screening and 30 days before; Oral/parenteral corticosteroid or NSAIDs (≤10 mg prednisone) administration at least 30 days before screening. Signed Informed consent  Exclusion Criteria:  Unstable knee; Varus or valgus ≥ 15 degrees; Active malignancy; Knee trauma or lose body parts 1 year before screening; Rheumatoid Arthritis, avascular necrosis, fibromyalgia; Use of potent analgesics 15 days (different from ≤ 10 mg prednisone) before screening; Intra-articular HA, polymerized polynucleotides or corticosteroid injection within 6 months before screening; Arthroscopic or knee open surgery within 12 months before screening; Body Mass Index (BMI) ≥ 40 kg/m2; Active infection around the injection site; Use of anticoagulants or history of thrombocytopenia; Concomitant use of disease-modifying antirheumatic drugs (DMARDs), anaesthetics; Known sensitivity to polymerized polynucleotides; Pregnancy, breast feeding.