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)

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-02-01 DOI:10.1016/j.nmd.2025.105275

Bettina C. Henzi , Niveditha Putananickal , Simone Schmidt , Sara Nagy , Daniela Rubino–Nacht , Sabine Schaedelin , Helge Amthor , Anne–Marie Childs , Nicolas Deconinck , Iain Horrocks , Saskia Houwen–van Opstal , Vincent Laugel , Mercedes Lopez Lobato , Andrés Nascimento Osorio , Ulrike Schara–Schmidt , Stefan Spinty , Arpad von Moers , Fiona Lawrence , Patricia Hafner , Olivier M. Dorchies , Dirk Fischer

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Abstract

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 non-ambulant 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).

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他莫昔芬治疗杜氏肌营养不良患者的安全性和有效性：一项多中心、随机、双盲、安慰剂对照的3期试验（TAMDMD B组）。

大多数杜氏肌营养不良症（DMD）患者不能走动。保持近端运动功能是至关重要的，但很少研究。他莫昔芬，一种选择性雌激素受体调节剂，在DMD小鼠模型中减少了肌肉病理的迹象。我们的目的是评估他莫昔芬在非活动DMD患者中超过48周的安全性和有效性。在这项多中心、随机、双盲、安慰剂对照的3期试验中，6个欧洲中心的10-16岁遗传诊断为DMD的男孩，非动态和非皮质类固醇治疗≥6个月，随机分配（1:1）口服他莫昔芬20mg /天或安慰剂。主要结果是D2运动功能测量从基线到第48周的变化。在筛查的15例非门诊男性DMD患者中，有14例于2019年1月24日至2021年1月6日入组。8名患者被随机分配到治疗组，6名患者被分配到安慰剂组。他莫昔芬和安慰剂的主要疗效结局无显著差异（7.8个百分点，95% CI, -26.82至11.22,p=0.359），其趋势不利于他莫昔芬。未发生死亡或危及生命的严重ae。他莫昔芬是安全的，但由于临床证据不足，不能推荐作为DMD的治疗选择。试验注册：ClinicalTrials.gov （NCT03354039）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.