Treatment for Patients With Osteoarthritis (OA)

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Systemic AMG 108 in Subjects With Osteoarthritis (OA)

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