Clinical trials in pediatric ALS: a TRICALS feasibility study

Tessa Kliest (1) , Ruben P.A. van Eijk (1) , Ammar Al-Chalabi (2, 3) , Alberto Albanese (4) , Peter Andersen (5) , Maria del Mar Amador (6) , Geir Bråthen , Veronique Brunaud-Danel (7) , Lev Brylev (8) , William Camu (9) , Mamede de Carvalho (10) , Cristina Cereda , Hakan Cetin (11) , Delia Chaverri (12) , Adriano Chiò (13) , Philippe Corcia (14) , Philippe Couratier (15, 16, 17) , Fabiola de Marchi (18) , Claude Desnuelle (19) , Michael van Es (1) , Jesús Esteban (20) , Massimiliano Filosto (21) , Alberto García Redondo (20) , Julian Grosskreutz (22) , Clemens Hanemann (23) , Trygve Holmøy (24, 25) , Helle Høyer (26) , Caroline Ingre (27) , Blaz Koritnik (28) , Magdalena Kuzma-Kozakiewicz (29) , Thomas Lambert (30) , Peter Leigh (31) , Christian Lunetta , Jessica Mandrioli (32) , Christopher Mcdermott (33) , Thomas Meyer , Jesus Mora (34) , Susanne Petri (35) , Mónica Povedano (36) , Evy Reviers (37) , Nilo Riva (38) , Kit C.B. Roes (39) , Miguel Á. Rubio (40) , François Salachas (6) , Stayko Sarafov (41) , Gianni Sorarù (42) , Zorica Stevic (43) , Kirsten Svenstrup (44) , Anette Torvin Møller (45) , Martin Turner (46) , Philip van Damme (47) , Lucie A.G. van Leeuwen (1) , Luis Varona (48) , Juan Vázquez Costa (49) , Markus Weber (50) , Orla Hardiman (51) , Leonard van den Berg (1)

1 Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht
2 Maurice Wohl Clinical Neuroscience Institut
3 KCH - King's College Hospital
4 Department Neurological Sciences, Milan University, IRCCS Humanitas Clinical Institute, Rozzano, M
5 Umeå University
6 CHU Pitié-Salpêtrière [AP-HP]
7 Université de Lille
8 Ministry of Healthcare of Russian Federation
9 Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital, Montpellier
10 Université de Lisbonne
11 Medizinische Universität Wien = Medical University of Vienna
12 Hospital Universitario La Paz
13 UNITO - Università degli studi di Torino = University of Turin
14 SLA CHRU Tours - Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours]
15 EpiMaCT - Epidémiologie des Maladies Chroniques en zone tropicale
16 Service de Neurologie [CHU Limoges]
17 SLA CHU Limoges - Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges]
18 Neurology Clinic, University Hospital “Maggiore della Carità”, Novara
19 CHU - Hôpital Pasteur [Nice]
20 Centro de Diagnóstico de Enfermedades Moleculares, Dpto. Biol. Mol. Centro de Biología Molecular-SO UAM-CSIC. Universidad Autónoma Madrid, Campus Cantoblanco; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Car
21 UniBs - Università degli Studi di Brescia = University of Brescia
22 Lubeck University Hospital
23 Peninsula Schools of Medicine and Dentistry
24 UiO - University of Oslo
25 Akershus University Hospital [Lørenskog]
26 Telemark Hospital Trust [Skien, Norway]
27 Karolinska Institutet, Department of Neurology
28 UMCL - University Medical Centre Ljubljana [Ljubljana, Slovenia]
29 MEDICAL UNIVERSITY OF WARSAW - Departement de Neurology
30 University Hospitals of North Midlands NHS Trust, Royal Stoke Hospital, Stoke-on-Trent, United Kingdom.
31 University of Sussex
32 University of Modena and Reggio Emilia, Department of Biomedical Sciences
33 Department of Neuroscience, Academic Neurology Unit, University of Sheffield
34 Sant Rafael Hospital
35 Department of Neurology, Hannover Medical School
36 Bellvitge University Hospital = Bellvitge Hospital Universitari
37 Leuven University Hospitals
38 Division of Neuroscience, San Raffaele Scientific Institute
39 Radboud University Medical Center [Nijmegen]
40 IMIM-Hospital del Mar
41 Medical University of Sofia [Bulgarie]
42 Université de Padoue
43 Institute of Neurology, Clinical Center of Serbia, University of Belgrade, Belgrade
44 UCPH - University of Copenhagen = Københavns Universitet
45 Aarhus University Hospital
46 University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, UK
47 University Hospitals Leuven [Leuven]
48 Servicio de Neurología, Hospital de Cruces, Barakaldo, Vizcaya
49 Neurology Service, Hospital Universitario La Fe, Valencia
50 KSSG - Cantonal Hospital St Gallen
51 Department of Neurology, The Adelaide and Meath Hospital, Trinity College Dublin

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.

Domaines: Santé publique et épidémiologie

Tessa Kliest, Ruben P.A. van Eijk, Ammar Al-Chalabi, Alberto Albanese, Peter Andersen, et al.. Clinical trials in pediatric ALS: a TRICALS feasibility study. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022, pp.1-8. ⟨10.1080/21678421.2021.2024856⟩. ⟨hal-03673852⟩