A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee

In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score.In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively).The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed.This study is registered with ClinicalTrials.gov with the identifier NCT00110942.Osteoarthritis (OA) is a chronic, painful, and potentially disabling disease of the joints that is manifested by cartilage damage, changes in the underlying bone, and varying degrees of synovial inflammation. The prevalence of OA increases with age; 60% to 70% of individuals aged 70 to 80 years have pathologic evidence of OA [1].The exact cause of OA is unknown. Recent debate suggests that cytokines produced by activated synovial cells or articular cartilage may be as