LY2951742, a Monoclonal Antibody Against CGRP, Failed to Reduce Signs and Symptoms of Knee Osteoarthritis

Purpose: LY2951742 (LY) is a neutralizing antibody of calcitonin-gene-related peptide (CGRP) that reduced joint pain in multiple animal models. A phase 2 study was conducted to test the efficacy and safety of LY in patients with moderate to severe knee pain due to osteoarthritis (OA). Methods: This study was a double blind, double dummy, placebo and active-controlled clinical trial in patients with mild to moderate knee OA (Kellgren-Lawrence grade 2 and 3 on knee X-ray), moderate to severe knee pain that worsened after their analgesic treatment was discontinued. Patients were randomized to placebo, celecoxib and 4 different doses of LY (5, 50, 120 and 300 mg) in a 2:1:1:1:1:1 ratio. LY or matching placebo was administered as subcutaneous injections twice 4 weeks apart. Celecoxib (200 mg) or matching placebo was administered orally once daily for 16 weeks. The primary efficacy endpoint was the change from baseline (CFBL) WOMAC Pain subscale rated with a 0–100mm visual analogue scale after 8-week treatment. A Bayesian dose-response longitudinal model was used, and the study would be considered positive if Pr (active treatment-Placebo<0) ≥0.95, and Pr (active treatment-placebo