Double-blind, randomized study to evaluate efficacy, and safety of fulranumab in patients with moderate to severe, chronic knee pain from osteoarthritis: interim analysis results

Abstract

Efficacy and safety of fulranumab, an anti-nerve growth factor (NGF) monoclonal antibody, was evaluated in a phase 2, active- and placebo-controlled, randomized study in patients with osteoarthritis. Patients (aged 40 to 80 years), with moderate to severe chronic knee pain from osteoarthritis were randomized (1:1:1:1) to placebo, fulranumab 3- or 9-mgQ4week, or oxycodone controlled-release (CR) 20 to 50mg bid. After washout from prior analgesic medications, patients entered a 16-week double-blind efficacy phase. Due to US FDA clinical hold on anti-NGF trials, including fulranumab (December 23, 2010), only 196 of 300 planned patients were enrolled and included in this interim analysis (completed double-blind phase:39, withdrawn:50, ongoing in double-blind phase:107). Efficacy results were based on data obtained through the cut-off date (28 December 2010). Safety results were based on data collected before and for 6 months after the cut-off date. Primary efficacy endpoint was the responder rate curve from baseline to week 12 of double-blind phase between each fulranumab group versus placebo and oxycodone CR. Both fulranumab groups showed significant improvement in pain relief in the responder analysis versus oxycodone CR (nominal p-values: 0.008 [3mgQ4wk]; 0.012 [9mgQ4wk]); neither fulranumab group separated statistically from placebo group (nominal p-values: 3mgQ4wk = 0.74, 9mgQ4wk = 0.84), which had a high response rate. Mean changes in average pain intensity scores from baseline to week 12 were consistent with the primary endpoint results: -3.0 (placebo and fulranumab 9mgQ4), -2.9 (fulranumab 3mgQ4), and -1.6 (oxycodone CR). Rates of treatment-emergent adverse events (TEAEs) were: 63% (fulranumab 3mgQ4), 82% (fulranumab 9mgQ4), 80% (oxycodone CR), and 77% (placebo). The most common (≥10%) TEAEs for total fulranumab-treated patients were headache and nasopharyngitis. Fulranumab demonstrated better pain relief in these patients than oxycodone CR, but failed to separate statistically from placebo. Fulranumab was generally well tolerated in the studied patient population. Efficacy and safety of fulranumab, an anti-nerve growth factor (NGF) monoclonal antibody, was evaluated in a phase 2, active- and placebo-controlled, randomized study in patients with osteoarthritis. Patients (aged 40 to 80 years), with moderate to severe chronic knee pain from osteoarthritis were randomized (1:1:1:1) to placebo, fulranumab 3- or 9-mgQ4week, or oxycodone controlled-release (CR) 20 to 50mg bid. After washout from prior analgesic medications, patients entered a 16-week double-blind efficacy phase. Due to US FDA clinical hold on anti-NGF trials, including fulranumab (December 23, 2010), only 196 of 300 planned patients were enrolled and included in this interim analysis (completed double-blind phase:39, withdrawn:50, ongoing in double-blind phase:107). Efficacy results were based on data obtained through the cut-off date (28 December 2010). Safety results were based on data collected before and for 6 months after the cut-off date. Primary efficacy endpoint was the responder rate curve from baseline to week 12 of double-blind phase between each fulranumab group versus placebo and oxycodone CR. Both fulranumab groups showed significant improvement in pain relief in the responder analysis versus oxycodone CR (nominal p-values: 0.008 [3mgQ4wk]; 0.012 [9mgQ4wk]); neither fulranumab group separated statistically from placebo group (nominal p-values: 3mgQ4wk = 0.74, 9mgQ4wk = 0.84), which had a high response rate. Mean changes in average pain intensity scores from baseline to week 12 were consistent with the primary endpoint results: -3.0 (placebo and fulranumab 9mgQ4), -2.9 (fulranumab 3mgQ4), and -1.6 (oxycodone CR). Rates of treatment-emergent adverse events (TEAEs) were: 63% (fulranumab 3mgQ4), 82% (fulranumab 9mgQ4), 80% (oxycodone CR), and 77% (placebo). The most common (≥10%) TEAEs for total fulranumab-treated patients were headache and nasopharyngitis. Fulranumab demonstrated better pain relief in these patients than oxycodone CR, but failed to separate statistically from placebo. Fulranumab was generally well tolerated in the studied patient population.