Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.
| Title: | Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. |
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| Authors: | Paganoni S; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts.; Fournier CN; Department of Neurology, Emory University, Atlanta, Georgia.; Macklin EA; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Biostatistics Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston.; Chibnik LB; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Biostatistics Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston.; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Quintana M; Berry Consultants LLC, Austin, Texas.; Saville BR; Berry Consultants LLC, Austin, Texas.; Detry MA; Berry Consultants LLC, Austin, Texas.; Vestrucci M; Berry Consultants LLC, Austin, Texas.; Marion J; Berry Consultants LLC, Austin, Texas.; McGlothlin A; Berry Consultants LLC, Austin, Texas.; Ajroud-Driss S; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Chase M; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Pothier L; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Harkey BA; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Yu H; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Sherman AV; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Shefner JM; Barrow Neurological Institute, Phoenix, Arizona.; Hall M; Barrow Neurological Institute, Phoenix, Arizona.; Kittle G; Barrow Neurological Institute, Phoenix, Arizona.; Berry JD; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Babu S; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Andrews J; Department of Neurology, Columbia University, New York, New York.; Dagostino D; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Tustison E; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Giacomelli E; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Scirocco E; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Alameda G; Phil Smith Neuroscience Institute, Holy Cross Hospital, Silver Spring, Maryland.; Locatelli E; Phil Smith Neuroscience Institute, Holy Cross Hospital, Silver Spring, Maryland.; Department of Neurology, Nova Southeastern University, Fort Lauderdale, Florida.; Ho D; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.; Quick A; Department of Neurology, Ohio State University, Columbus.; Katz J; California Pacific Medical Center and Forbes Norris MDA-ALS Research and Treatment Center, San Francisco.; Heitzman D; Texas Neurology, Dallas.; Appel SH; Methodist Neurological Institute, Houston, Texas.; Shroff S; Methodist Neurological Institute, Houston, Texas.; Felice K; Department of Neuromuscular Medicine, Hospital for Special Care, New Britain, Connecticut.; Maragakis NJ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Simmons Z; Department of Neurology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.; Miller TM; Department of Neurology, Hope Center for Neurological Disorders, Washington University in St Louis, St Louis, Missouri.; Olney N; Providence ALS Clinic, Portland, Oregon.; Weiss MD; Department of Neurology, University of Washington Medical Center, Seattle.; Goutman SA; Department of Neurology, University of Michigan, Ann Arbor.; Fernandes JA; Department of Neurology, University of Nebraska Medical Center, Omaha.; Jawdat O; Departmennt of Neurology, University of Kansas Medical Center, Kansas City.; Owegi MA; Department of Neurology, University of Massachusetts Medical School, Worcester.; Foster LA; Department of Neurology, University of Colorado School of Medicine, Aurora.; Vu T; Department of Neurology, University of South Florida, Tampa.; Ilieva H; Jefferson Weinberg ALS Center, Philadelphia, Pennsylvania.; Newman DS; Henry Ford Health System Department of Neurology, Detroit, Michigan.; Arcila-Londono X; Henry Ford Health System Department of Neurology, Detroit, Michigan.; Jackson CE; Department of Neurology, University of Texas Health, San Antonio.; Ladha S; Barrow Neurological Institute, Phoenix, Arizona.; Heiman-Patterson T; Department of Neurology, Temple Health, Philadelphia, Pennsylvania.; Caress JB; Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.; Swenson A; Department of Neurology, University of Iowa, Iowa City.; Peltier A; Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.; Lewis R; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.; Fee D; Department of Neurology, Medical College of Wisconsin, Milwaukee.; Elliott M; Department of Neurology, University of Virginia, Arlington.; Bedlack R; Department of Neurology, Duke University, Durham, North Carolina.; Kasarskis EJ; Department of Neurology, University of Kentucky, Lexington.; Elman L; Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia.; Rosenfeld J; Department of Neurology, Loma Linda University School of Medicine, Loma Linda, California.; Walk D; Department of Neurology, University of Minnesota/Twin Cities ALS Research Consortium, Minneapolis and St Paul.; McIlduff C; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.; Twydell P; Department of Neurology, Spectrum Health Medical Group, Grand Rapids, Michigan.; Young E; Department of Neurology, SUNY (State University of New York) Upstate, Syracuse.; Johnson K; Department of Neurology, Ochsner Health System, New Orleans, Louisiana.; Rezania K; Department of Neurology, University of Chicago, Chicago, Illinois.; Goyal NA; Department of Neurology, University of California, Irvine, Medical Center.; Cohen JA; Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.; Benatar M; Department of Neurology, University of Miami, Miami, Florida.; Jones V; Department of Physical Medicine and Rehabilitation, School of Medicine, University of Missouri, Columbia.; Glass J; Department of Neurology, Emory University, Atlanta, Georgia.; Shah J; Department of Neurology, Mayo Clinic, Jacksonville, Florida.; Beydoun SR; Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles.; Wymer JP; Department of Neurology, University of Florida, Gainesville.; Zilliox L; Department of Neurology, University of Maryland School of Medicine, Baltimore.; Nayar S; Department of Neurology, Georgetown University, Washington, DC.; Pattee GL; Neurology Associates, Lincoln, Nebraska.; Martinez-Thompson J; Department of Neurology, Mayo Clinic, Rochester, Minnesota.; Harvey B; UCB Pharma, Cambridge, Massachusetts.; Patel S; UCB Pharma, Cambridge, Massachusetts.; Mahoney P; UCB, Slough, United Kingdom.; Duda PW; UCB Pharma, Cambridge, Massachusetts.; Cudkowicz ME; Sean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston. |
| Corporate Authors: | HEALEY ALS Platform Trial Study Group |
| Source: | JAMA network open [JAMA Netw Open] 2025 Feb 03; Vol. 8 (2), pp. e2459058. Date of Electronic Publication: 2025 Feb 03. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase III; Clinical Trial, Phase II; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101729235 Publication Model: Electronic Cited Medium: Internet ISSN: 2574-3805 (Electronic) Linking ISSN: 25743805 NLM ISO Abbreviation: JAMA Netw Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago, IL : American Medical Association, [2018]- |
| MeSH Terms: | Amyotrophic Lateral Sclerosis*/drug therapy; Humans ; Male ; Female ; Middle Aged ; Double-Blind Method ; Aged ; Treatment Outcome |
| Abstract: | Importance: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression.; Objective: To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS.; Design, Setting, and Participants: Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens.; Interventions: Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing.; Main Outcomes and Measures: The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; |
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| Contributed Indexing: | Investigator: DD Hayden; PY Lai; RA Donahue; HW Chen; J Wang; N Mathai; G Lopes; A McCaffrey; J Scalia; S Luppino; C Lagier-Tourenne; G Sadri-Vakili; S Kolb; S Heintzman; R Sufit; A Szymanski; L Jenkins; A Martin; E Simpson Greene; JR Thonhoff; B Liao; CD Whitaker; LL Clawson; A Uchil; KM Riley; J Arneklev; J Grogan; X Su; M Mamarabadi; A Malcolm; T Bazan; N Rad; LH Wang; EL Feldman; E Piccione; P Thaisetthawatkul; C Farmakidis; D Jabari; J Statland; M Pasnoor; M Dimachkie; RH Brown; M Ghasemi; H Houmani; C Douthwright; K Daniello; N Suresh; J Farias; IA Chen; P Pasinelli; K Steijlen; R Bhavaraju-Sanka; B Jacobsen; J Milliard; R Bowser; A Deboo; MS Cartwright; C Nance; L Gutmann; J Yasek; M Harms; M Burford; F Diaz; D Shrilla; G Rakocevic; S Jones; G Solorzano; X Li; Z Mahuwala; VVM Kumaraswamy; C Quinn; M Baer; D Borg; K Bhuvaneswaran; J Kaur; S Maiser; SB Rutkove; A Mundwiler; JA Meyer; P Rao; B Soliven; R Roos; AA Habib; T Mozaffar; MK Korb; J Mullen; E Stommel; NM Robbins; N Carberry; V Granit; R Govindarajan; B Oskarsson; L Darki; R Rodriguez; M Chuquilin; W McNeely; M Diaz-Abad; PH Jin; C Chauhan; J Bobenhouse; NP Staff; G Hayat; L Arroyave; A Bailey; J Bailey; V Barlow; A Bulat; G Changkuon; M Cirino; C Deignan; E Deirmendjian; A De Mattos; S DiStefano; K Drake; M Estes; K Faulconer; P Figueroa-Szostek; T Garozzo; MG Hasenoehrl; J Henrique; N Henrique; S Hurwitz; C Igne; L Irwin; K Jentoft; B Jordan; I Katsovskiy; O Kharakozova; T Kolvek; A Korin; T La; H Li; J Nguyen; I Novak; R Ortiz; J Ostrow; J Pagliaro; J Palillo; P Patel; J Patterson; M Phan; N Popel; S Proueng; J Rosenthal; C Small; N Tarasenko; M Thomas; P Vigneswaran; Y Wahab; I Whitworth; S Wright; M Connolly; D De Santiago; A Felix; K Garrett; J Hamilton; K Khan; M Lovett; L Nelson; M Pabon; D Rede; P Bolger; A Fetouh; J Woodcook; C Kamp; J Kennedy; A McGarry; M Torti |
| Molecular Sequence: | ClinicalTrials.gov NCT04297683 |
| Entry Date(s): | Date Created: 20250217 Date Completed: 20250217 Latest Revision: 20260206 |
| Update Code: | 20260206 |
| PubMed Central ID: | PMC11833520 |
| DOI: | 10.1001/jamanetworkopen.2024.59058 |
| PMID: | 39960672 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase III; Clinical Trial, Phase II; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural