A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial

Finkel, Richard S.; McDonald, Craig M.; Sweeney, H. Lee; Finanger, Erika; Knierbein, Erin Neil; Wagner, Kathryn R.; Mathews, Katherine D.; Marks, Warren; Statland, Jeffrey; Nance, Jessica; McMillan, Hugh J.; McCullagh, Gary; Tian, Cuixia; Ryan, Monique M.; O'Rourke, Declan; Mueller-Felber, Wolfgang; Tulinius, Mar; Burnette, W. Bryan; Nguyen, Cam-Tu; Vijayakumar, Kayal; Johannsen, Jessika; Phan, Han C.; Eagle, Michelle; MacDougall, James; Mancini, Maria und Donovan, Joanne M. (2021): A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. In: Journal of Neuromuscular Diseases, Bd. 8, Nr. 5: S. 769-784

Abstract

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-kappa B and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD). Objective: This international, randomized 2 : 1, placebo-controlled, phase 3 study in patients >= 4-< 8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks. Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA;primary) and timed function tests (TFTs;secondary). Assessment of health-related function used the Pediatric Outcomes Data Collection tool (PODCI). Results: One hundred thirty one patients received edasalonexent (n = 88) and placebo (n = 43). At week 52, differences between edasalonexent and placebo for NSAA total score and TFTs were not statistically significant, although there were consistently less functional declines in the edasalonexent group. A pre-specified analysis by age demonstrated that younger patients (<= 6.0 years) showed more robust and statistically significant differences between edasalonexent and placebo for some assessments. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly involved the gastrointestinal system (primarily diarrhea). Conclusions: Edasalonexent was generally well-tolerated with a manageable safety profile at the dose of 100 mg/kg/day. Although edasalonexent did not achieve statistical significance for improvement in primary and secondary functional end-points for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2214-3599
• Sprache: Englisch