Y Jin1, C Smith2, D Monteith3, R Brown4, A Camporeale5, T A McNearney6, M A Deeg7, E Raddad8, N Xiao9, A de la Peña10, A J Kivitz11, T J Schnitzer12. 1. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: jin_yan_yj@lilly.com. 2. Eli Lilly and Company, Erl Wood Manor, Windlesham, UK. Electronic address: csmith@lilly.com. 3. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: dkmonteit@gmail.com. 4. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: brownrk60@gmail.com. 5. Eli Lilly Italia SpA, 50019 Sesto Fiorentino (FI), Italy. Electronic address: camporeale_angelo@lilly.com. 6. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: tmcnearn@yahoo.com. 7. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: mdeeg@regulusrx.com. 8. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: eyas@lilly.com. 9. Novartis, Cambridge, MA, USA. Electronic address: xiao.ni@novartis.com. 10. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: adelapa@lilly.com. 11. Altoona Center for Clinical Research, Duncansville, PA, USA. Electronic address: ajkivitz@yahoo.com. 12. Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. Electronic address: tjs@northwestern.edu.
Abstract
OBJECTIVE: This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain. METHOD: In a multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for 16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks, twice. The primary outcome was change from baseline at Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by 100 mm visual analog scale (VAS). The trial was considered positive if ≥1 dose of galcanezumab demonstrated ≥95% Bayesian posterior probability of superiority to placebo and ≥50% posterior probability of superiority to placebo by ≥9 mm. A planned interim analysis allowed termination of the study if posterior probability of superiority to placebo by ≥9 mm was ≤5%. Secondary endpoints included WOMAC function subscore and Patient Global Assessment (PGA) of OA. Safety and tolerability were also assessed. RESULTS: The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reduced WOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified success criteria. No improvement in any secondary objective was observed. Galcanezumab was well tolerated by OA patients. CONCLUSIONS: This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain. STUDY IDENTIFICATION: NCT02192190.
RCT Entities:
OBJECTIVE: This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain. METHOD: In a multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for 16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks, twice. The primary outcome was change from baseline at Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by 100 mm visual analog scale (VAS). The trial was considered positive if ≥1 dose of galcanezumab demonstrated ≥95% Bayesian posterior probability of superiority to placebo and ≥50% posterior probability of superiority to placebo by ≥9 mm. A planned interim analysis allowed termination of the study if posterior probability of superiority to placebo by ≥9 mm was ≤5%. Secondary endpoints included WOMAC function subscore and Patient Global Assessment (PGA) of OA. Safety and tolerability were also assessed. RESULTS: The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reduced WOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified success criteria. No improvement in any secondary objective was observed. Galcanezumab was well tolerated by OA patients. CONCLUSIONS: This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain. STUDY IDENTIFICATION: NCT02192190.
Authors: Seungyup Sun; Nicklaus H Diggins; Zachary J Gunderson; Jill C Fehrenbacher; Fletcher A White; Melissa A Kacena Journal: Bone Date: 2019-11-09 Impact factor: 4.398
Authors: Meagan J Makarczyk; Qi Gao; Yuchen He; Zhong Li; Michael S Gold; Mark C Hochberg; Bruce A Bunnell; Rocky S Tuan; Stuart B Goodman; Hang Lin Journal: Tissue Eng Part C Methods Date: 2021-02-04 Impact factor: 3.056