This is a double-blind, prospective, randomized study in which patients will be randomized to 1 of 5 treatment arms (4 active and 1 placebo).

Each patient will receive one SC injection of REGN475 or placebo and 1 IV infusion of either REGN475 or placebo, on day 1 (baseline) In order to preserve the blind, patients receiving REGN475 SC will also receive placebo IV, and patients receiving REGN475 IV will also receive placebo SC.

Inclusion Criteria:

1. Diagnosis of OA of the knee according to American College of Rheumatology (ACR) criteria, and experiencing moderate to severe pain in the index knee for at least 3 months prior to the screening visit.
2. Kellgren-Lawrence grade 2-3 radiographic severity of the index knee at or within 6 months prior to Screening.

Exclusion Criteria:

1. Significant concomitant illness including, but not limited to, cardiac, renal, neurological, endocrinological, metabolic or lymphatic disease that would adversely affect the patient's participation in the study.
2. Patients with joint replacement in the affected knee.
3. Intra-articular injection of corticosteroids or hyaluronic acid in the affected knee within the 3 months prior to the screening visit.
4. Women who are pregnant or breast-feeding.