This is a Phase 2 study, involving a 4-week treatment period, designed to test the ability of investigational study drug ARRY-371797 to reduce pain in patients with moderate to severe pain due to osteoarthritis (OA) of the knee, and to further evaluate the drug's safety. Approximately 150 patients from the US will be enrolled in this study.

Key Inclusion Criteria:

• Diagnosis of OA of the knee, based on American College of Rheumatology (ACR) criteria, confirmed by X-ray (K-L Grade II/III within the last year).
• At least moderate or severe pain due to OA in one knee.
• On nonsteroidal anti-inflammatory drug (NSAID) 28 days previous to study start and willing to continue on NSAID throughout study.
• Discontinuation of opioids prior to study start.
• Additional criteria exist.

Key Exclusion Criteria:

• Current or recent infection in the last 7 days; infection requiring hospitalization or parenteral antibiotics within the last 6 months; history of or currently active tuberculosis, hepatitis B or C, or human immunodeficiency virus (HIV).
• Surgery on the index knee within the previous 6 months.
• Trauma or other surgeries within the previous 8 weeks.
• Specific abnormal laboratory values or electrocardiogram abnormalities.
• Gastrointestinal surgery that may interfere with motility or absorption.
• On non-stable dose of bisphosphonates, or any prior denosumab or parathyroid hormone (PTH) therapies.
• Prior parenteral tumor necrosis factor (TNF) inhibitor or anti-nerve growth factor (NGF) therapies.
• Intramuscular, intravenous or oral corticosteroids within the previous 6 weeks.
• Intra-articular corticosteroids in the index knee within the previous 8 weeks or viscosupplementation in the index knee within the previous 4 months.
• Currently enrolled in or participated in another clinical trial within the previous 3 months.
• Additional criteria exist.