Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B)
Por:
Henzi BC, Putananickal N, Schmidt S, Nagy S, Rubino-Nacht D, Schaedelin S, Amthor H, Childs AM, Deconinck N, Horrocks I, Houwen-van Opstal S, Laugel V, Lobato ML, Nascimento-Osorio A, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM and Fischer D
Publicada:
1 feb 2025
Ahead of Print:
1 ene 2025
Resumen:
Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model. Our objective was to assess the safety and efficacy of tamoxifen over 48 weeks in non-ambulant DMD patients. In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at six European centres boys aged 10-16 years with genetically diagnosed DMD, non-ambulant and off corticosteroid treatment for >= 6 months, randomly assigned (1:1) to either 20 mg/day tamoxifen orally or placebo were included. The primary outcome was change in D2 motor function measure from baseline to week 48. Of 15 nonambulant male patients with DMD screened, 14 were enrolled from January 24th, 2019, to January 6th, 2021. Eight patients were randomised to the treatment and six to the placebo group. The primary efficacy outcome did not differ significantly between tamoxifen and placebo (7.8 percentage points, 95 % CI, -26.82 to 11.22, p = 0.359) with a trend not favouring tamoxifen. No deaths or life-threatening serious AEs occurred. Tamoxifen was safe but due to insufficient clinical evidence, it cannot be recommended as a treatment option for DMD. Trial registration: ClinicalTrials.gov (NCT03354039).
Filiaciones:
Henzi BC:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Division of Neuropediatrics, Development and Rehabilitation, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Putananickal N:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Schmidt S:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Nagy S:
Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland
Rubino-Nacht D:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Schaedelin S:
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland
Amthor H:
Service de Neurologie et Réanimation Pédiatriques, APHP Paris Saclay, Hôpital Raymond Poincaré, 92380, Garches, France
Childs AM:
The Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
Deconinck N:
Department of Paediatric Neurology and Neuromuscular Reference Center, Hôpital Universitaire des Enfants Reine Fabiola (HUB), Université Libre de Bruxelles, Brussels, Belgium
Horrocks I:
Royal Hospital for Children, Glasgow, United Kingdom
Houwen-van Opstal S:
Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
Laugel V:
Department of Pediatric Neurology, Strasbourg University Hospital, Strasbourg, France
Lobato ML:
Sección de Neurología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, España
Nascimento-Osorio A:
Neuromuscular Unit, Department of Neurology, Hospital Sant Joan de Déu and Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
Schara-Schmidt U:
Department of Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Spinty S:
Alder Hey Children's Hospital, Liverpool, United Kingdom
von Moers A:
Department of Pediatrics, DRK Kliniken Berlin Westend, Berlin, Germany
Lawrence F:
Duchenne UK, London, United Kingdom
Hafner P:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Dorchies OM:
School of Pharmaceutical Sciences, University of Geneva, Switzerland
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland
Fischer D:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Green Submitted, Bronze
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