Clinical trials in pediatric ALS: a TRICALS feasibility study

Area of Science:

• Neurology
• Pediatric Medicine
• Clinical Pharmacology

Background:

• Pediatric Investigation Plans (PIPs) mandate pediatric drug studies for European marketing authorization.
• In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory in Europe.
• Waivers can be granted by the European Medicines Agency (EMA) under certain conditions.

Purpose of the Study:

• To evaluate the feasibility of conducting clinical studies on ALS therapies in children (<18 years) in Europe.
• To assess the prevalence and recruitment potential for pediatric ALS in Europe.
• To gather expert opinions on the necessity of waivers for pediatric ALS research.

Main Methods:

• Searched the EMA database for submitted PIPs related to ALS.
• Distributed a questionnaire to 58 European ALS centers regarding pediatric ALS prevalence and trial recruitment.
• Collected expert opinions on waivers for pediatric ALS studies.

Main Results:

• Four PIPs for ALS were identified; two were waived, and two are planned.
• The prevalence of pediatric ALS (onset <18 years) was found to be extremely low (0.008 per 100,000).
• Estimated recruitment potential across 47 centers was only 26 pediatric patients within five years, with 75.5% of experts favoring a waiver.

Conclusions:

• Pediatric ALS is exceptionally rare and may represent a distinct condition from adult ALS.
• Clinical trials for pediatric ALS face significant challenges including recruitment, cost, and trial design.
• The low prevalence strongly supports the recommendation for waivers for pediatric ALS studies.