@article{TEXTUAL,
      recid = {14639},
      author = {Paganoni, Sabrina and Fournier, Christina N. and Macklin,  Eric A. and Chibnik, Lori B. and Quintana, Melanie and  Saville, Benjamin R. and Detry, Michelle A. and Vestrucci,  Matteo and Marion, Joe and McGlothlin, Anna and  Ajroud-Driss, Senda and Chase, Marianne and Pothier,  Lindsay and Harkey, Brittney A. and Yu, Hong and Sherman,  Alexander V. and Shefner, Jeremy M. and Hall, Meghan and  Kittle, Gale and Berry, James D. and Rezania, Kourosh},
      title = {Efficacy and Safety of Zilucoplan in Amyotrophic Lateral  Sclerosis: A Randomized Clinical Trial},
      journal = {JAMA Network Open},
      address = {2025-02-17},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;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.&lt;/p&gt;  &lt;p&gt;Objective: To determine the effects of zilucoplan, an  inhibitor of complement C5, in individuals with ALS.&lt;/p&gt;  &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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; &lt;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).&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt; &lt;p&gt;Trial Registration:  ClinicalTrials.gov Identifier: &lt;a  href="https://clinicaltrials.gov/study/NCT04297683"  target="_blank"&gt;NCT04297683&lt;/a&gt;&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/14639},
}