Journal article
A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial
Journal of neuromuscular diseases, Vol.8(5), pp.769-784
06/10/2021
DOI: 10.3233/JND-210689
PMCID: PMC8543277
PMID: 34120912
Abstract
Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB 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 = 81) or placebo (n = 38). 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 endpoints for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age. (NCT03703882)
Details
- Title: Subtitle
- A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial
- Creators
- Richard S Finkel - St. Jude Children’s Research Hospital, Memphis, TN and Nemours Children’s Hospital, Orlando, FLCraig M McDonald - University of California at Davis, Sacramento, CAH Lee Sweeney - University of Florida College of Medicine, Gainesville, FLErika Finanger - Shriners Hospital for Children, Portland, ORErin Neil Knierbein - University of Michigan, MI, Ann Arbor, MIKathryn R Wagner - Kennedy Krieger Institute, The Johns Hopkins School of Medicine, Baltimore, MDKatherine D Mathews - University of Iowa, Stead Family Department of PediatricsWarren Marks - Cook Children’s Medical Center, Fort Worth, TXJeffrey Statland - University of Kansas Medical Center, Kansas City, KSJessica Nance - Johns Hopkins University, Baltimore, MDHugh J McMillan - Children’s Hospital of Eastern Ontario, Ottawa, CAGary McCullagh - Royal Manchester Children’s Hospital, UKCuixia Tian - Cincinnati Children’s Hospital & University of Cincinnati, Cincinnati, OHMonique M Ryan - Royal Children’s Hospital, Melbourne, AustraliaDeclan O’Rourke - Children’s Health Ireland at Temple Street, Dublin, IrelandWolfgang Müller-Felber - Dr. v. Haunersches Kinderspital, Munich, GermanyMar Tulinius - Queen Silvia Children’s Hospital, Gothenburg, SwedenW Bryan Burnette - Vanderbilt University Medical Center, Nashville, TNCam-Tu Nguyen - CHU Sainte-Justine, Montreal, CAKayal Vijayakumar - Bristol Children’s Hospital, Bristol, UKJessika Johannsen - University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHan C Phan - Rare Disease Research, LLC, Atlanta GA, Hamburg, GermanyMichelle Eagle - Atom International Limited, Newcastle upon Tyne, UKJames MacDougall - University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMaria Mancini - Catabasis Pharmaceuticals, Inc., Boston, MAJoanne M Donovan - Catabasis Pharmaceuticals, Inc., Boston, MAPolarisDMD Study Group
- Resource Type
- Journal article
- Publication Details
- Journal of neuromuscular diseases, Vol.8(5), pp.769-784
- DOI
- 10.3233/JND-210689
- PMID
- 34120912
- PMCID
- PMC8543277
- NLM abbreviation
- J Neuromuscul Dis
- ISSN
- 2214-3599
- eISSN
- 2214-3602
- Language
- English
- Date published
- 06/10/2021
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984085471802771
Metrics
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