This is a randomized, placebo-controlled, double-blind study in which 500 patients with osteoarthritis (OA) knee pain will be randomized to Ampion or placebo and followed for 20 weeks. The clinical effects of treatment on OA pain will be evaluated during clinic visits at 6, 12, and 20 weeks using WOMAC® osteoarthritis Index and the Patient's Global Assessment of disease severity (PGA). Safety will be assessed by recording adverse events, concomitant medications, physical examination, vital signs and clinical laboratory tests.