Evidence map›Paper›PMID 39960672›Full record

Trial reportJAMA network open2025

Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Sabrina Paganoni, Christina N Fournier, Eric A Macklin, Lori B Chibnik, Melanie Quintana, Benjamin R Saville, Michelle A Detry, Matteo Vestrucci, Joe Marion, Anna McGlothlin and 76 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA network open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04297683 (HEALEY ALS Platform Trial), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04297683 phase2 / phase3active not recruitingnot on this map

HEALEY ALS Platform Trial

TypeinterventionalSponsorMerit E. Cudkowicz, MDRan2020 to 2028Enrolled1,500ConditionsAmyotrophic Lateral SclerosisArmsZilucoplan, Verdiperstat, CNM-Au8, Pridopidine, SLS-005 Trehalose
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

86 authors.

Sabrina PaganoniSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Christina N FournierDepartment of Neurology, Emory University, Atlanta, Georgia.
Eric A MacklinSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Lori B ChibnikSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Melanie QuintanaBerry Consultants LLC, Austin, Texas.
Benjamin R SavilleBerry Consultants LLC, Austin, Texas.
Michelle A DetryBerry Consultants LLC, Austin, Texas.
Matteo VestrucciBerry Consultants LLC, Austin, Texas.
Joe MarionBerry Consultants LLC, Austin, Texas.
Anna McGlothlinBerry Consultants LLC, Austin, Texas.
Senda Ajroud-DrissDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Marianne ChaseSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Lindsay PothierSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Brittney A HarkeySean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Hong YuSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Alexander V ShermanSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Jeremy M ShefnerBarrow Neurological Institute, Phoenix, Arizona.
Meghan HallBarrow Neurological Institute, Phoenix, Arizona.
Gale KittleBarrow Neurological Institute, Phoenix, Arizona.
James D BerrySean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Suma BabuSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Jinsy AndrewsDepartment of Neurology, Columbia University, New York, New York.
Derek DagostinoSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Eric TustisonSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Elisa GiacomelliSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Erica SciroccoSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Gustavo AlamedaPhil Smith Neuroscience Institute, Holy Cross Hospital, Silver Spring, Maryland.
Eduardo LocatelliPhil Smith Neuroscience Institute, Holy Cross Hospital, Silver Spring, Maryland.
Doreen HoSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
Adam QuickDepartment of Neurology, Ohio State University, Columbus.
Jonathan KatzCalifornia Pacific Medical Center and Forbes Norris MDA-ALS Research and Treatment Center, San Francisco.
Daragh HeitzmanTexas Neurology, Dallas.
Stanley H AppelMethodist Neurological Institute, Houston, Texas.
Sheetal ShroffMethodist Neurological Institute, Houston, Texas.
Kevin FeliceDepartment of Neuromuscular Medicine, Hospital for Special Care, New Britain, Connecticut.
Nicholas J MaragakisDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Zachary SimmonsDepartment of Neurology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
Timothy M MillerDepartment of Neurology, Hope Center for Neurological Disorders, Washington University in St Louis, St Louis, Missouri.
Nicholas OlneyProvidence ALS Clinic, Portland, Oregon.
Michael D WeissDepartment of Neurology, University of Washington Medical Center, Seattle.
Stephen A GoutmanDepartment of Neurology, University of Michigan, Ann Arbor.
Joseph Americo FernandesDepartment of Neurology, University of Nebraska Medical Center, Omaha.
Omar JawdatDepartmennt of Neurology, University of Kansas Medical Center, Kansas City.
Margaret Ayo OwegiDepartment of Neurology, University of Massachusetts Medical School, Worcester.
Laura A FosterDepartment of Neurology, University of Colorado School of Medicine, Aurora.
Tuan VuDepartment of Neurology, University of South Florida, Tampa.
Hristelina IlievaJefferson Weinberg ALS Center, Philadelphia, Pennsylvania.
Daniel S NewmanHenry Ford Health System Department of Neurology, Detroit, Michigan.
Ximena Arcila-LondonoHenry Ford Health System Department of Neurology, Detroit, Michigan.
Carlayne E JacksonDepartment of Neurology, University of Texas Health, San Antonio.
Shafeeq LadhaBarrow Neurological Institute, Phoenix, Arizona.
Terry Heiman-PattersonDepartment of Neurology, Temple Health, Philadelphia, Pennsylvania.
James B CaressDepartment of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Andrea SwensonDepartment of Neurology, University of Iowa, Iowa City.
Amanda PeltierDepartment of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee.
Richard LewisDepartment of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.
Dominic FeeDepartment of Neurology, Medical College of Wisconsin, Milwaukee.
Matthew ElliottDepartment of Neurology, University of Virginia, Arlington.
Richard BedlackDepartment of Neurology, Duke University, Durham, North Carolina.
Edward J KasarskisDepartment of Neurology, University of Kentucky, Lexington.
Lauren ElmanDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia.
Jeffrey RosenfeldDepartment of Neurology, Loma Linda University School of Medicine, Loma Linda, California.
David WalkDepartment of Neurology, University of Minnesota/Twin Cities ALS Research Consortium, Minneapolis and St Paul.
Courtney McIlduffDepartment of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Paul TwydellDepartment of Neurology, Spectrum Health Medical Group, Grand Rapids, Michigan.
Eufrosina YoungDepartment of Neurology, SUNY (State University of New York) Upstate, Syracuse.
Kristin JohnsonDepartment of Neurology, Ochsner Health System, New Orleans, Louisiana.
Kourosh RezaniaDepartment of Neurology, University of Chicago, Chicago, Illinois.
Namita A GoyalDepartment of Neurology, University of California, Irvine, Medical Center.
Jeffrey A CohenDepartment of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Michael BenatarDepartment of Neurology, University of Miami, Miami, Florida.
Vovanti JonesDepartment of Physical Medicine and Rehabilitation, School of Medicine, University of Missouri, Columbia.
Jonathan GlassDepartment of Neurology, Emory University, Atlanta, Georgia.
Jaimin ShahDepartment of Neurology, Mayo Clinic, Jacksonville, Florida.
Said R BeydounDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles.
James P WymerDepartment of Neurology, University of Florida, Gainesville.
Lindsay ZillioxDepartment of Neurology, University of Maryland School of Medicine, Baltimore.
Shakti NayarDepartment of Neurology, Georgetown University, Washington, DC.
Gary L PatteeNeurology Associates, Lincoln, Nebraska.
Jennifer Martinez-ThompsonDepartment of Neurology, Mayo Clinic, Rochester, Minnesota.
Brittany HarveyUCB Pharma, Cambridge, Massachusetts.
Shital PatelUCB Pharma, Cambridge, Massachusetts.
Paul MahoneyUCB, Slough, United Kingdom.
Petra W DudaUCB Pharma, Cambridge, Massachusetts.
Merit E CudkowiczSean M. Healey & AMG Center for ALS and the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston.
HEALEY ALS Platform Trial Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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; <1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164). Results: Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. Conclusions and Relevance: In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. Trial Registration: ClinicalTrials.gov Identifier: NCT04297683.

Indexed as

Amyotrophic Lateral SclerosisAgedDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment Outcome

Identifiers

PMID39960672
PMCPMC11833520

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.