Clinical trials in pediatric ALS: a TRICALS feasibility study.

Abstract

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.

• Authors: Tessa Kliest, Ruben P A Van Eijk, Ammar Al-Chalabi, Alberto Albanese, Peter M Andersen, Maria Del Mar Amador, Geir BrÅthen, Veronique Brunaud-Danel, Lev Brylev, William Camu, Mamede De Carvalho, Cristina Cereda, Hakan Cetin, Delia Chaverri, Adriano Chiò, Philippe Corcia, Philippe Couratier, Fabiola De Marchi, Claude Desnuelle, Michael A Van Es, JesÚs Esteban, Massimiliano Filosto, Alberto GarcÍa Redondo, Julian Grosskreutz, Clemens O Hanemann, Trygve HolmØy, Helle HØyer, Caroline Ingre, Blaz Koritnik, Magdalena Kuzma-Kozakiewicz, Thomas Lambert, Peter N Leigh, Christian Lunetta, Jessica Mandrioli, Christopher J Mcdermott, Thomas Meyer, Jesus S Mora, Susanne Petri, MÓnica Povedano, Evy Reviers, Nilo Riva, Kit C B Roes, Miguel Á Rubio, FranÇois Salachas, Stayko Sarafov, Gianni SorarÙ, Zorica Stevic, Kirsten Svenstrup, Anette Torvin MØller, Martin R Turner, Philip Van Damme, Lucie A G Van Leeuwen, Luis Varona, Juan F VÁzquez Costa, Markus Weber, Orla Hardiman, Leonard H Van Den Berg
• Journal: Amyotrophic lateral sclerosis & frontotemporal degeneration (Amyotroph Lateral Scler Frontotemporal Degener) Vol. 23 Issue 7-8 Pg. 481-488 (Nov 2022) ISSN: 2167-9223 [Electronic] England
• PMID: 35172656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Child
• Humans
• Amyotrophic Lateral Sclerosis (diagnosis, epidemiology, therapy)
• Feasibility Studies
• Europe
• Databases, Factual
• Prevalence