The purpose of this study is to evaluate the clinical benefit (change in Western Ontario and McMaster University Osteoarthritis Index [WOMAC] pain score) of AMG 108 (300 mg subcutaneously [SC] every 4 weeks) in subjects with OA.

Inclusion Criteria:

• Diagnosed with knee OA as determined by American College of Rheumatology (ACR) criteria
• Pain defined by a level of greater than or equal to 30 mm on a 100 mm Visual Analogue Scale (VAS)
• If currently taking any over the counter nutritional supplements, must be on stable doses for greater than 2 months prior to screening
• If utilizing physical therapy, biomechanical devices or orthotic support, must have been using treatment or device for greater than or equal to 2 months prior to screening
• If currently or previously taking any non-prescribed supplement (e.g., glucosamine or chondroitin sulphate, shark cartilage, diacerein, soya extract, etc.) must be on stable doses for at least 2 months prior to screening
• If currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), must be on stable doses for at least 2 months prior to screening
• Able to discontinue NSAIDs at least 5 half-lives (approximately 3 days) prior to Day 1
• Radiographic evidence of tibio-femoral compartment knee OA within 12 months of screening
• Signed written informed consent

Exclusion Criteria:

• Malignancy within the previous 5 years, except for basal cell or in situ cancer
• Significant hematologic disease - Active infection or history of recurrent or chronic infections
• Known diagnosis of HIV, hepatitis B, or hepatitis C infection
• Uncontrolled diabetes or cardiovascular disease and hypertension
• Inflammatory arthropathy including secondary OA
• Isolated OA of the patellofemoral joint (bi or tri-compartmental involvement are not exclusions)
• End-stage ("bone-on-bone") OA (Kellgren Lawrence score of 4)
• OA of the hip ipsilateral to the index knee - Total white cell count less than 2.0 x 10^9/L and/or platelet count less than 100 x 10^9/L observed within 1 month preceding screening
• Prior intra-articular (IA) injection of anakinra or experimental interleukin-1 (IL-1) inhibitor therapy - Concurrent treatment with SC anakinra
• Concurrent or recent (less than or equal to 1 month) use of experimental therapy
• Prior IA corticosteroid injection within 1 month of study
• Prior viscosupplement therapy within 3 months of study
• Contraindication(s) to IA injections
• Subjects who are pregnant or breast-feeding, or plan to become pregnant during the study
• Subject is not using adequate contraception
• Known allergy to E coli-derived products
• Unable to understand informed consent
• Concerns regarding subject's compliance with the protocol procedures
• Subject will not be available for follow-up assessment
• Active substance abuse