Prostatic Diseases and Male Voiding Dysfunction Preliminary Assessment of Safety and Efficacy in Proof-of-Concept, Randomized Clinical Trial of Tanezumab for Chronic Prostatitis/Chronic Pelvic Pain Syndrome J. Curtis Nickel, Gary Atkinson, John N. Krieger, Ian W. Mills, Michel Pontari, Daniel A. Shoskes, and Tim J. Crook OBJECTIVE To assess the efficacy and safety of tanezumab, a humanized monoclonal antibody directed against the pain-mediating neurotrophin, nerve growth factor, to treat pain and other symptoms of chronic prostatitis/chronic pelvic pain syndrome in a Phase IIa, proof-of-concept clinical trial powered to provide 2-sided 90% confidence interval around the primary endpoint. METHODS Patients received a single intravenous dose of tanezumab (20 mg) or placebo. The primary efficacy endpoint was the change from baseline to week 6 in average daily numerical rating scale pain score. The secondary endpoints included the change from baseline to week 6 in the National Institutes of Health Chronic Prostatitis Symptom Index and urinary symptoms. Safety was also assessed. RESULTS Overall, 62 patients were randomized (30 to tanezumab and 32 to placebo). At week 6, tanezumab marginally improved the average daily pain (least-squares mean difference from placebo -0.47, 90% confidence interval -1.150-0.209) and urgency episode frequency (least- squares mean difference from placebo -1.37, 90% confidence interval -3.146-0.401). No difference was seen in the National Institutes of Health chronic prostatitis symptom index total score or micturition frequency at week 6. The most common adverse events were paresthesia and arthralgia. The odds of having a 30% reduction in pain were 1.75-fold greater (90% confidence interval 0.65-4.69) for patients receiving tanezumab versus placebo. CONCLUSION Tanezumab might improve symptoms for some patients with chronic prostatitis/chronic pelvic pain syndrome. Although proof of concept was not demonstrated in the present study, additional studies with larger populations and stricter inclusion criteria according to patient phenotype might identify populations in which antinerve growth factor treatment will provide clinical benefit. UROLOGY 80: 1105–1110, 2012. © 2012 Elsevier Inc. C hronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents the most common chronic prostatitis syndrome, affecting approxi- mately 10% of adults. 1 CP/CPPS is characterized by genital or pelvic pain, associated with voiding or sexual dysfunction, lasting 3 months. 2 Patients with CP/CPPS have no evidence of active bacterial urinary tract infec- tion. 3 CP/CPPS symptoms diminish quality of life and impair both physical and psychological function. 4 Treat- ment of CP/CPPS includes antibiotics, anti-inflammato- ries, analgesics, muscle relaxants (including -blockers 5 ), and many other empirical therapies. However, these are often inadequate for many patients, indicating an urgent need to develop novel and effective therapies. 4 Nerve growth factor (NGF) is a neurotrophin released from mast cells 6 that is an important mediator of pain transduction mechanisms of nociceptive neurons. Al- Financial Disclosure: J. C. Nickel is a consultant/investigator for GlaxoSmithKline, Johnson & Johnson, Pfizer, Inc., Watson Pharmaceuticals, Ferring Pharmaceuticals, Tocris Bioscience, Farr Laboratories, Astellas Pharma, Triton Pharma, Trillium Therapeutics, and Eli Lilly; M. Pontari is a consultant for Eli Lilly and Azcan; D. A. Shoskes is a consultant for Farr Laboratories and an investor in, and receives compensation from, Triurol; G. Atkinson, I. W. Mills, and T. J. Crook are employees of, and hold stock or options, in Pfizer, Inc. J. N. Krieger declares that he has no relevant financial interests. Funding Support: This study was sponsored by Pfizer, Inc.; editorial/medical writing support was provided by Joseph Oleynek of UBC Scientific Solutions and was funded by Pfizer, Inc. From the Department of Urology, Queen’s University, Kingston, Ontario, Canada; Pfizer Pharmaceuticals, Inc., Sandwich, Kent, United Kingdom; Department of Urol- ogy, University of Washington, Seattle, WA; Department of Urology, Temple Uni- versity, Philadelphia, PA; and Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH Reprint requests: J. Curtis Nickel, M.D., F.R.C.S.C., Department of Urology, Queen’s University, Kingston, ON, K7L 2V7 Canada. E-mail: jcn@queensu.ca Submitted: June 3, 2012, accepted (with revisions): July 21, 2012 © 2012 Elsevier Inc. 0090-4295/12/$36.00 1105 All Rights Reserved http://dx.doi.org/10.1016/j.urology.2012.07.035