Abstract Details

Title 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

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 11-010

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

Results n/a

Conclusions

Utreloxastat is currently under evaluation in CARDINALS, a clinical trial in patients with ALS.

Authors/Disclosures
Jeremy M. Shefner, MD, PhD, FAAN (Barrow Neurological Institute) PRESENTER	Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Uniqure. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene. Dr. Shefner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cytokinetics. Dr. Shefner has received personal compensation in the range of $0-$499 for serving as a Consultant for Mitsubishi Tanabe Pharma America. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for annexon. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurosense. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuvivo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nura BIo. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prilenia. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for swanbio. Dr. Shefner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vertex. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Shefner has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. The institution of Dr. Shefner has received research support from NIH. The institution of Dr. Shefner has received research support from Mitsubishi Tanabe Pharma America. The institution of Dr. Shefner has received research support from Amylyx. The institution of Dr. Shefner has received research support from BIogen. The institution of Dr. Shefner has received research support from Cytokinetics. The institution of Dr. Shefner has received research support from IONIS. The institution of Dr. Shefner has received research support from Healey Center for ALS. Dr. Shefner has received personal compensation in the range of $500-$4,999 for serving as a grant review chair with DOD- General Dynamics.
Jonathan S. Katz, MD (CPMC)	Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Calico. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenyx. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Katz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Griffols. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Tuan H. Vu, MD (University of South Florida)	Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen (Horizon). Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Vu has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Alexion. The institution of Dr. Vu has received research support from RA Pharma/UCB. The institution of Dr. Vu has received research support from Mass Gen Hospital/Healy Platform Study. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Horizon/Amgen. The institution of Dr. Vu has received research support from Woolsey Pharma. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Cartesian Therapeutics. The institution of Dr. Vu has received research support from Janssen/Johnson & Johnson. The institution of Dr. Vu has received research support from Immunovant. The institution of Dr. Vu has received research support from Regeneron. The institution of Dr. Vu has received research support from Dianthus. The institution of Dr. Vu has received research support from COUR.
Adriano Chio, MD, FAAN (Dept. of Neuroscience, University of Turin)	Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept.
Christopher McDermott	The institution of Christopher McDermott has received research support from NIHR. The institution of Christopher McDermott has received research support from Motor Neurone Disease Association.
David Devos (Service De Neurologie Du Pr. Desteee)	The institution of Mr. Devos has received research support from Alterity.
Mayzie Johnston (PTC)	No disclosure on file
Rafael Sierra, PhD (Allergan)	Dr. Sierra has received personal compensation for serving as an employee of PTC Therapeutics Inc. Dr. Sierra has stock in PTC Therapeutics Inc.
Aaron Tansy, MD	Dr. Tansy has received personal compensation for serving as an employee of PTC Therapeutics, Inc.. Dr. Tansy has stock in PTC Therapeutics, Inc..
Jeff Trimmer (PTC Therapeutics)	No disclosure on file

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