CARDINALS: A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Utreloxastat (PTC857) in Patients with Amyotrophic Lateral Sclerosis
Jonathan S Katz1, Tuan Vu2, Adriano Chio3, Christopher McDermott4, David Devos5, Mayzie Johnston6, Rafael Sierra6, Aaron Tansy6, Jeff Trimmer6, Jeremy M Shefner7
1Forbes Norris MDA/ALS Research and Treatment Center, 2University of South Florida, 3Dept. of Neuroscience, University of Turin, 4Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, 5Service De Neurologie Du Pr. Desteee, 6PTC Therapeutics, Inc, 7Barrow Neurological Institute, University of Arizona
Objective:
CARDINALS (NCT05349721) is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy, safety, tolerability, pharmacokinetics, and biomarker effects of utreloxastat in patients with ALS.
Background:
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of motor neurons. The pathophysiology underlying ALS has been mechanistically linked with ferroptosis, a form of programmed cell death due to iron-dependent excess accumulation of lipid peroxides and oxidative stress. Utreloxastat (PTC857) is an emerging, orally bioavailable small molecule for the treatment of ALS that inhibits 15-lipoxygenase (15-LO) enzyme and the downstream products leading to ferroptosis in neurodegenerative disease.
Design/Methods:
This study will enroll patients with ALS aged 18–80 years with a diagnosis of definite or probable ALS of ≤24 months of symptoms, a total ALSFRS-R score ≥34 and no significant respiratory compromise. The study comprises an 8-week screening period followed by a 24-week double-blind treatment period, where ~258 eligible patients will be randomized 2:1 to receive utreloxastat 250 mg or placebo twice daily. Following the double-blind period, eligible patients will have the option to enter a ≥28-week long-term open-label extension period where they will receive utreloxastat. The primary objective is to evaluate the efficacy of utreloxastat vs placebo in slowing disease progression assessed by the change in ALSFRS-R score after 24 weeks. Secondary and exploratory objectives include safety and tolerability, respiratory function, pharmacokinetics, biomarker effects, and health-related quality of life. CARDINALS is currently recruiting patients
Conclusions:
Utreloxastat is currently under evaluation in CARDINALS, a clinical trial in patients with ALS.