Safety and efficacy of tamoxifen in patients with duchenne muscular dystrophy: open label extension of TAMDMD trial
Por:
Zwingli G, 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, Lopez Lobato M, Nascimento-Osorio A, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM, Fischer D and Henzi BC
Publicada:
1 abr 2026
Ahead of Print:
1 feb 2026
Resumen:
Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy was assessed in the double-blind, randomised, placebo-controlled, multicenter phase 3 trial (TAMDMD), which was followed by an 48 weeks open label extension study. The aim of the open label extension study was to investigate if earlier initiation of tamoxifen could reduce the progression of the disease compared to delayed initiation of tamoxifen. Of the initial TAMDMD trial participants, 66 patients were enrolled in the open label extension (OLE). The objective was to investigate the efficacy of prolonged treatment with tamoxifen 20 mg daily, adjunct to corticosteroids, in individuals with DMD over 48 weeks. We aimed to analyse the sustained effect and the timing effect of tamoxifen in patients with DMD on the basis of a set of motor function tests. The sustained effect corresponds to the treatment effect seen in the tamoxifen treatment arm of the RCT phase of the trial being sustained after all patients got the treatment in the OLE phase. The timing effect addresses if patients with earlier tamoxifen initiation show more favourable disease trajectory than patients with delayed tamoxifen initiation. This study was registered with ClinicalTrials.gov (NCT03354039). Between May 28th 2019 and July 28th 2021, 66 patients in 10 study centres in seven European countries could be enrolled into the OLE phase. Of those, 32 had previously been treated with tamoxifen and 34 had been assigned to placebo. The efficacy outcome defined as the change in the motor function did not differ significantly between the early tamoxifen treatment group and the delayed tamoxifen treatment group. There was neither a sustained nor a timing effect of tamoxifen. Overall tamoxifen was well tolerated. No deaths or life-threatening serious adverse events occurred. The OLE phase of the TAMDMD trial showed that treatment with tamoxifen continued to be well tolerated overall; however, there was neither a sustained nor a timing effect of tamoxifen treatment in patients with DMD. We cannot provide statistical nor clinical evidence that prolonged treatment with tamoxifen is effective in delaying disease progression in DMD when used as an adjunct to corticosteroids.
Filiaciones:
Zwingli G:
Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, 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
Lopez Lobato M:
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:
INSERM U1055, Laboratory of Fundamental and Applied Bioenergetics, Université Grenoble-Alpes, Grenoble, France
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
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
Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Rehabil, Nijmegen, Netherlands
Univ Duisburg Essen, Univ Hosp Essen, Dept Pediat Neurol, Essen, Germany
DRK Kliniken Berlin Westend, Dept Pediat, Berlin, Germany
Green Submitted, hybrid
|