First-in-human randomized clinical trials of the safety and efficacy of tanezumab for treatment of chronic knee osteoarthritis pain or acute bunionectomy pain

Abstract. Introduction:. The neurotrophin nerve growth factor has a demonstrated role in pain transduction and pathophysiology. Objectives:. Two randomized, double-blind, placebo-controlled, phase 1 studies were conducted to evaluate safety, tolerability, and analgesic efficacy of single doses of tanezumab, a humanized anti–nerve growth factor monoclonal antibody, in chronic or acute pain. Methods:. In the first study (CL001), patients with moderate to severe pain from osteoarthritis (OA) of the knee received a single intravenous infusion of tanezumab (3–1000 μg/kg) or placebo in a dose-escalation (part 1; N = 42) or parallel-arm (part 2; N = 79) study design. The second study (CL002) was a placebo-controlled dose-escalation (tanezumab 10–1000 μg/kg; N = 50) study in patients undergoing bunionectomy surgery. Results:. Adverse event rates were generally similar across treatments. Most adverse events were generally mild to moderate in severity and no patients discontinued as a result of adverse events. Adverse events of abnormal peripheral sensation were more common with higher doses of tanezumab (≥100 μg/kg) than with placebo. These were generally mild to moderate in severity. Tanezumab provided up to 12 weeks of effective analgesia for OA knee pain, with statistically significant improvements at doses ≥100 μg/kg (P < 0.05). By contrast, no trend for analgesic activity was found when tanezumab was administered 8 to 16 hours before bunionectomy. Conclusions:. The demonstration of a favorable safety profile and clinical efficacy in OA pain supports clinical development of tanezumab as a potential treatment for chronic pain conditions