Search: onr:"swepub:oai:DiVA.org:umu-226731" > Safety and efficacy...
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000 | 16145naa a2201813 4500 | |
001 | oai:DiVA.org:umu-226731 | |
003 | SwePub | |
008 | 240624s2024 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-2267312 URI |
024 | 7 | a https://doi.org/10.1016/S1474-4422(24)00134-02 DOI |
040 | a (SwePub)umu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
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100 | 1 | a Benatar, Michaelu Department of Neurology, University of Miami Miller School of Medicine, FL, Miami, United States4 aut |
245 | 1 0 | a Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) :b a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial |
264 | 1 | b Elsevier,c 2024 |
338 | a print2 rdacarrier | |
520 | a Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
700 | 1 | a Hansen, Thomasu Orphazyme, Copenhagen, Denmark4 aut |
700 | 1 | a Rom, Droru Prosoft Clinical, PA, Chesterbrook, United States4 aut |
700 | 1 | a Geist, Marie Au Orphazyme, Copenhagen, Denmark4 aut |
700 | 1 | a Blaettler, Thomasu Orphazyme, Copenhagen, Denmark4 aut |
700 | 1 | a Camu, Williamu Department of Neurology University of Montpellier, CHU Montpellier, INM INSERM, Montpellier, France4 aut |
700 | 1 | a Kuzma-Kozakiewicz, Magdalenau Department of Neurology, Medical University of Warsaw, Warsaw, Poland4 aut |
700 | 1 | a van den Berg, Leonard Hu Department of Neurology, University Medical Center Utrecht, Utrecht, Netherlands4 aut |
700 | 1 | a Morales, Raul Juntasu Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain4 aut |
700 | 1 | a Chio, Adrianou Rita Levi Montalcini Department of Neuroscience, University of Torino, Torino, Italy4 aut |
700 | 1 | a Andersen, Peter M.,d 1962-u Umeå universitet,Neurovetenskaper4 aut0 (Swepub:umu)pean0001 |
700 | 1 | a Pradat, Pierre-Francoisu APHP, Department of Neurology, Hôpital Pitié-Salpêtrière, Paris, France4 aut |
700 | 1 | a Lange, Daleu Department of Neurology, Hospital for Special Surgery, NY, New York, United States4 aut |
700 | 1 | a Van Damme, Philipu Department of Neurology, University Hospital Leuven, KU Leuven, Leuven, Belgium4 aut |
700 | 1 | a Mora, Gabrieleu Istituti Clinici Scientifici Maugeri, IRCCS Milano, Milan, Italy4 aut |
700 | 1 | a Grudniak, Mariuszu Research and Development Department, Polish Stem Cell Bank, Warsaw, Poland4 aut |
700 | 1 | a Elliott, Matthewu University of Virginia Medical Center, VA, Charlottesville, United States4 aut |
700 | 1 | a Petri, Susanneu Department of Neurology, Hannover Medical School, Hannover, Germany4 aut |
700 | 1 | a Olney, Nicholasu Providence Portland Medical Center, Providence Brain and Spine Institute, OR, Portland, United States4 aut |
700 | 1 | a Ladha, Shafeequ Department of Neurology, Barrow Neurological Institute, AZ, Phoenix, United States4 aut |
700 | 1 | a Goyal, Namita Au Department of Neurology, University of California Irvine, CA, Irvine, United States4 aut |
700 | 1 | a Meyer, Thomasu Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany4 aut |
700 | 1 | a Hanna, Michael Gu University College London, National Hospital for Neurology and Neurosurgery, London, United Kingdom4 aut |
700 | 1 | a Quinn, Colinu Department of Neurology, Perelman School of Medicine, University of Pennsylvania, PA, Philadelphia, United States4 aut |
700 | 1 | a Genge, Angelau Department of Neurology, Montreal Neurological Institute, QC, Montreal, Canada4 aut |
700 | 1 | a Zinman, Lorneu Sunnybrook Health Sciences Centre, ON, Toronto, Canada4 aut |
700 | 1 | a Jabari, Duaau Department of Neurology, The University of Kansas Medical Center, KS, Kansas City, United States4 aut |
700 | 1 | a Shoesmith, Christenu Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, ON, London, Canada4 aut |
700 | 1 | a Ludolph, Albert Cu Department of Neurology, University of Ulm, Ulm, Germany4 aut |
700 | 1 | a Neuwirth, Christophu Neuromuscular Disease Unit/ALS Clinic, Kantonspital St Gallen, St Gallen, Switzerland4 aut |
700 | 1 | a Nations, Sharonu University of Texas Southwestern, TX, Dallas, United States4 aut |
700 | 1 | a Shefner, Jeremy Mu Department of Neurology, Barrow Neurological Institute, AZ, Phoenix, United States4 aut |
700 | 1 | a Turner, Martin Ru Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom4 aut |
700 | 1 | a Wuu, Joanneu Department of Neurology, University of Miami Miller School of Medicine, FL, Miami, United States4 aut |
700 | 1 | a Bennett, Richardu Orphazyme, Copenhagen, Denmark4 aut |
700 | 1 | a Dang, Hoangu Orphazyme, Copenhagen, Denmark4 aut |
700 | 1 | a Sundgreen, Clausu Orphazyme, Copenhagen, Denmark4 aut |
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710 | 2 | a Department of Neurology, University of Miami Miller School of Medicine, FL, Miami, United Statesb Orphazyme, Copenhagen, Denmark4 org |
773 | 0 | t Lancet Neurologyd : Elsevierg 23:7, s. 687-699q 23:7<687-699x 1474-4422x 1474-4465 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-226731 |
856 | 4 8 | u https://doi.org/10.1016/S1474-4422(24)00134-0 |
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