Evaluation of Acebilustat, a Selective Inhibitor of Leukotriene B4 Biosynthesis, for Treatment of Outpatients With Mild-Moderate Coronavirus Disease 2019: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

{ 'indexed': {'date-parts': [[2023, 12, 7]], 'date-time': '2023-12-07T08:37:20Z', 'timestamp': 1701938240401}, 'reference-count': 38, 'publisher': 'Oxford University Press (OUP)', 'issue': '2', 'license': [ { 'start': { 'date-parts': [[2023, 3, 30]], 'date-time': '2023-03-30T00:00:00Z', 'timestamp': 1680134400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://academic.oup.com/pages/standard-publication-reuse-rights'}], 'funder': [ {'DOI': '10.13039/100005492', 'name': 'Stanford University', 'doi-asserted-by': 'publisher'}, {'name': 'Celltaxis'}, { 'DOI': '10.13039/100016220', 'name': 'CTSA', 'doi-asserted-by': 'publisher', 'award': ['UL1 TR003142']}, {'DOI': '10.13039/100000002', 'name': 'NIH', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2023, 7, 26]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>The vast majority of coronavirus disease 2019 (COVID-19) disease ' 'occurs in outpatients where treatment is limited to antivirals for high-risk subgroups. ' 'Acebilustat, a leukotriene B4 inhibitor, has potential to reduce inflammation and symptom ' 'duration.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>In a single-center trial spanning Delta and Omicron variants, ' 'outpatients were randomized to 100 mg/d of oral acebilustat or placebo for 28 days. Patients ' 'reported daily symptoms via electronic query through day 28 with phone follow-up on day 120 ' 'and collected nasal swab samples on days 1–10. The primary outcome was sustained symptom ' 'resolution to day 28. Secondary 28-day outcomes included time to first symptom resolution, ' 'area under the curve (AUC) for longitudinal daily symptom scores, duration of viral shedding ' 'through day 10, and symptoms on day 120.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Sixty participants were randomized to each study arm. At ' 'enrollment, the median duration was 4 days (interquartile range, 3–5 days), and the median ' 'number of symptoms was 9 (7–11). Most patients (90%) were vaccinated, with 73% having ' 'neutralizing antibodies. A minority of participants (44%; 35% in the acebilustat arm and 53% ' 'in placebo) had sustained symptom resolution at day 28 (hazard ratio, 0.6 [95% confidence ' 'interval, .34–1.04]; P = .07 favoring placebo). There was no difference in the mean AUC for ' 'symptom scores over 28 days (difference in mean AUC, 9.4 [95% confidence interval, −42.1 to ' '60.9]; P = .72). Acebilustat did not affect viral shedding or symptoms at day 120.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Sustained symptoms through day 28 were common in this low-risk ' 'population. Despite this, leukotriene B4 antagonism with acebilustat did not shorten symptom ' 'duration in outpatients with COVID-19.</jats:p>\n' ' <jats:p>Clinical Trials Registration. NCT04662060.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/cid/ciad187', 'type': 'journal-article', 'created': {'date-parts': [[2023, 3, 31]], 'date-time': '2023-03-31T02:01:43Z', 'timestamp': 1680228103000}, 'page': '186-193', 'source': 'Crossref', 'is-referenced-by-count': 1, 'title': 'Evaluation of Acebilustat, a Selective Inhibitor of Leukotriene B4 Biosynthesis, for Treatment ' 'of Outpatients With Mild-Moderate Coronavirus Disease 2019: A Randomized, Double-Blind, ' 'Placebo-Controlled Phase 2 Trial', 'prefix': '10.1093', 'volume': '77', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-5316-4971', 'authenticated-orcid': False, 'given': 'Joseph E', 'family': 'Levitt', 'sequence': 'first', 'affiliation': [ { 'name': 'Division of Pulmonary, Allergy, and Critical Medicine, ' 'Department of Medicine, Stanford University School of Medicine , ' 'Stanford, CA , USA'}]}, { 'given': 'Haley', 'family': 'Hedlin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Quantitative Sciences 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Allergy, and Critical Medicine, ' 'Department of Medicine, Stanford University School of Medicine , ' 'Stanford, CA , USA'}]}], 'member': '286', 'published-online': {'date-parts': [[2023, 3, 30]]}, 'reference': [ { 'key': '2023092304121090100_ciad187-B1', 'doi-asserted-by': 'crossref', 'first-page': '693', 'DOI': '10.1056/NEJMoa2021436', 'article-title': 'Dexamethasone in hospitalized patients with Covid-19', 'volume': '384', 'author': 'RECOVERY Collaborative Group', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': '2023092304121090100_ciad187-B2', 'doi-asserted-by': 'crossref', 'first-page': '5866', 'DOI': '10.1021/cr200246d', 'article-title': 'Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles ' 'in disease', 'volume': '111', 'author': 'Haeggstrom', 'year': '2011', 'journal-title': 'Chem Rev'}, { 'key': '2023092304121090100_ciad187-B3', 'doi-asserted-by': 'crossref', 'first-page': '1841', 'DOI': '10.1056/NEJMra071371', 'article-title': 'Leukotrienes', 'volume': '357', 'author': 'Peters-Golden', 'year': '2007', 'journal-title': 'N Engl J Med'}, { 'key': '2023092304121090100_ciad187-B4', 'doi-asserted-by': 'crossref', 'first-page': '264', 'DOI': '10.1038/286264a0', 'article-title': 'Leukotriene B, a potent chemokinetic and aggregating substance released ' 'from polymorphonuclear leukocytes', 'volume': '286', 'author': 'Ford-Hutchinson', 'year': '1980', 'journal-title': 'Nature'}, { 'key': '2023092304121090100_ciad187-B5', 'doi-asserted-by': 'crossref', 'first-page': '965', 'DOI': '10.1038/ni972', 'article-title': 'Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment ' 'to inflamed tissues', 'volume': '4', 'author': 'Goodarzi', 'year': '2003', 'journal-title': 'Nat Immunol'}, { 'key': '2023092304121090100_ciad187-B6', 'doi-asserted-by': 'crossref', 'first-page': '6562', 'DOI': '10.4049/jimmunol.1002400', 'article-title': 'Leukotriene B4 mediates neutrophil migration induced by heme', 'volume': '186', 'author': 'Monteiro', 'year': '2011', 'journal-title': 'J Immunol'}, { 'key': '2023092304121090100_ciad187-B7', 'doi-asserted-by': 'crossref', 'DOI': '10.1155/2012/536156', 'article-title': 'Circulating leukotriene B4 identifies respiratory complications after ' 'trauma', 'volume': '2012', 'author': 'Auner', 'year': '2012', 'journal-title': 'Mediators Inflamm'}, { 'key': '2023092304121090100_ciad187-B8', 'doi-asserted-by': 'crossref', 'first-page': '714', 'DOI': '10.1164/ajrccm/138.3.714', 'article-title': 'Increased concentrations of leukotrienes in bronchoalveolar lavage ' 'fluid of patients with ARDS or at risk for ARDS', 'volume': '138', 'author': 'Stephenson', 'year': '1988', 'journal-title': 'Am Rev Respir Dis'}, { 'key': '2023092304121090100_ciad187-B9', 'first-page': '194', 'article-title': 'Neutrophil priming and activation in the pathogenesis of postinjury ' 'multiple organ failure', 'volume': '4', 'author': 'Partrick', 'year': '1996', 'journal-title': 'New Horiz'}, { 'key': '2023092304121090100_ciad187-B10', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.ebiom.2020.102789', 'article-title': 'A glimpse into the eye of the COVID-19 cytokine storm', 'volume': '55', 'author': 'Kuppalli', 'year': '2020', 'journal-title': 'EBioMedicine'}, { 'key': '2023092304121090100_ciad187-B11', 'doi-asserted-by': 'crossref', 'first-page': '28', 'DOI': '10.1111/cts.12428', 'article-title': 'Phase I studies of acebilustat: biomarker response and safety in ' 'patients with cystic fibrosis', 'volume': '10', 'author': 'Elborn', 'year': '2017', 'journal-title': 'Clin Transl Sci'}, { 'key': '2023092304121090100_ciad187-B12', 'doi-asserted-by': 'crossref', 'first-page': '1026', 'DOI': '10.1016/j.jcf.2021.08.007', 'article-title': 'Empire-CF study: a phase 2 clinical trial of leukotriene A4 hydrolase ' 'inhibitor acebilustat in adult subjects with cystic fibrosis', 'volume': '20', 'author': 'Elborn', 'year': '2021', 'journal-title': 'J Cyst Fibros'}, { 'key': '2023092304121090100_ciad187-B13', 'doi-asserted-by': 'crossref', 'first-page': '20', 'DOI': '10.1111/cts.12426', 'article-title': 'Phase I studies of acebilustat: pharmacokinetics, pharmacodynamics, ' 'food effect, and CY:3A induction', 'volume': '10', 'author': 'Elborn', 'year': '2017', 'journal-title': 'Clin Transl Sci'}, { 'key': '2023092304121090100_ciad187-B14', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.cct.2021.106509', 'article-title': 'The COVID-19 Outpatient Pragmatic Platform Study (COPPS): study design ' 'of a multi-center pragmatic platform trial', 'volume': '108', 'author': 'Bunning', 'year': '2021', 'journal-title': 'Contemp Clin Trials'}, { 'key': '2023092304121090100_ciad187-B15', 'doi-asserted-by': 'crossref', 'first-page': '3329', 'DOI': '10.1002/sim.3710', 'article-title': 'Randomization by minimization for unbalanced treatment allocation', 'volume': '28', 'author': 'Han', 'year': '2009', 'journal-title': 'Stat Med'}, { 'key': '2023092304121090100_ciad187-B16', 'doi-asserted-by': 'crossref', 'DOI': '10.1126/sciimmunol.abe0240', 'article-title': 'Defining the features and duration of antibody responses to SARS-CoV-2 ' 'infection associated with disease severity and outcome', 'volume': '5', 'author': 'Roltgen', 'year': '2020', 'journal-title': 'Sci Immunol'}, { 'key': '2023092304121090100_ciad187-B17', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.jcv.2022.105242', 'article-title': 'Harmonization of SARS-CoV-2 reverse transcription quantitative PCR ' 'tests to the first WHO international standard for SARS-CoV-2 RNA', 'volume': '154', 'author': 'Sahoo', 'year': '2022', 'journal-title': 'J Clin Virol'}, { 'key': '2023092304121090100_ciad187-B18', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.jcv.2022.105101', 'article-title': 'Development and evaluation of an RT-qPCR for the identification of the ' 'SARS-CoV-2 omicron variant', 'volume': '148', 'author': 'Sibai', 'year': '2022', 'journal-title': 'J Clin Virol'}, { 'key': '2023092304121090100_ciad187-B19', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/JCM.00859-21', 'article-title': 'Multiplex SARS-CoV-2 genotyping reverse transcriptase PCR for ' 'population-level variant screening and epidemiologic surveillance', 'volume': '59', 'author': 'Wang', 'year': '2021', 'journal-title': 'J Clin Microbiol'}, { 'key': '2023092304121090100_ciad187-B20', 'doi-asserted-by': 'crossref', 'DOI': '10.1128/jcm.00178-22', 'article-title': 'Evaluation of a rapid and accessible reverse transcription-quantitative ' 'PCR approach for SARS-CoV-2 variant of concern identification', 'volume': '60', 'author': 'Yeung', 'year': '2022', 'journal-title': 'J Clin Microbiol'}, { 'key': '2023092304121090100_ciad187-B21', 'doi-asserted-by': 'crossref', 'first-page': '1883', 'DOI': '10.1093/cid/ciac312', 'article-title': 'Favipiravir for treatment of outpatients with asymptomatic or ' 'uncomplicated coronavirus disease 2019: a double-blind, randomized, ' 'placebo-controlled, phase 2 trial', 'volume': '75', 'author': 'Holubar', 'year': '2022', 'journal-title': 'Clin Infect Dis'}, { 'key': '2023092304121090100_ciad187-B22', 'doi-asserted-by': 'crossref', 'first-page': '1967', 'DOI': '10.1038/s41467-021-22177-1', 'article-title': 'Peginterferon lambda-1a for treatment of outpatients with uncomplicated ' 'COVID-19: a randomized placebo-controlled trial', 'volume': '12', 'author': 'Jagannathan', 'year': '2021', 'journal-title': 'Nat Commun'}, { 'key': '2023092304121090100_ciad187-B23', 'doi-asserted-by': 'crossref', 'first-page': '763', 'DOI': '10.1016/S2213-2600(21)00160-0', 'article-title': 'Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase ' '2, open-label, randomised controlled trial', 'volume': '9', 'author': 'Ramakrishnan', 'year': '2021', 'journal-title': 'Lancet Respir Med'}, { 'key': '2023092304121090100_ciad187-B24', 'doi-asserted-by': 'crossref', 'first-page': '42', 'DOI': '10.1001/jamainternmed.2021.6759', 'article-title': 'Efficacy of inhaled ciclesonide for outpatient treatment of adolescents ' 'and adults with symptomatic COVID-19: a randomized clinical trial', 'volume': '182', 'author': 'Clemency', 'year': '2022', 'journal-title': 'JAMA Intern Med'}, { 'key': '2023092304121090100_ciad187-B25', 'doi-asserted-by': 'crossref', 'first-page': '1010', 'DOI': '10.1016/j.cmi.2022.02.031', 'article-title': 'Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at ' 'risk of adverse outcomes: a randomised controlled trial (COVERAGE)', 'volume': '28', 'author': 'Duvignaud', 'year': '2022', 'journal-title': 'Clin Microbiol Infect'}, { 'key': '2023092304121090100_ciad187-B26', 'doi-asserted-by': 'crossref', 'first-page': '2292', 'DOI': '10.1001/jama.2020.22760', 'article-title': 'Fluvoxamine vs placebo and clinical deterioration in outpatients with ' 'symptomatic COVID-19: a randomized clinical trial', 'volume': '324', 'author': 'Lenze', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': '2023092304121090100_ciad187-B27', 'doi-asserted-by': 'crossref', 'first-page': 'e42', 'DOI': '10.1016/S2214-109X(21)00448-4', 'article-title': 'Effect of early treatment with fluvoxamine on risk of emergency care ' 'and hospitalisation among patients with COVID-19: the TOGETHER ' 'randomised, platform clinical trial', 'volume': '10', 'author': 'Reis', 'year': '2022', 'journal-title': 'Lancet Glob Health'}, {'key': '2023092304121090100_ciad187-B28', 'author': 'McCarthy', 'year': '1 2022'}, { 'key': '2023092304121090100_ciad187-B29', 'doi-asserted-by': 'crossref', 'first-page': '924', 'DOI': '10.1016/S2213-2600(21)00222-8', 'article-title': 'Colchicine for community-treated patients with COVID-19 (COLCORONA): a ' 'phase 3, randomised, double-blinded, adaptive, placebo-controlled, ' 'multicentre trial', 'volume': '9', 'author': 'Tardif', 'year': '2021', 'journal-title': 'Lancet Respir Med'}, { 'key': '2023092304121090100_ciad187-B30', 'doi-asserted-by': 'crossref', 'first-page': '1130', 'DOI': '10.1016/S2213-2600(21)00263-0', 'article-title': 'Azithromycin versus standard care in patients with mild-to-moderate ' 'COVID-19 (ATOMIC2): an open-label, randomised trial', 'volume': '9', 'author': 'Hinks', 'year': '2021', 'journal-title': 'Lancet Respir Med'}, { 'key': '2023092304121090100_ciad187-B31', 'doi-asserted-by': 'crossref', 'first-page': '490', 'DOI': '10.1001/jama.2021.11517', 'article-title': 'Effect of oral azithromycin vs placebo on COVID-19 symptoms in ' 'outpatients with SARS-CoV-2 infection: a randomized clinical trial', 'volume': '326', 'author': 'Oldenburg', 'year': '2021', 'journal-title': 'JAMA'}, { 'key': '2023092304121090100_ciad187-B32', 'doi-asserted-by': 'crossref', 'first-page': '879', 'DOI': '10.1136/gutjnl-2022-326952', 'article-title': 'Oral famotidine versus placebo in non-hospitalised patients with ' 'COVID-19: a randomised, double-blind, data-intense, phase 2 clinical ' 'trial', 'volume': '71', 'author': 'Brennan', 'year': '2022', 'journal-title': 'Gut'}, { 'key': '2023092304121090100_ciad187-B33', 'doi-asserted-by': 'crossref', 'first-page': '472', 'DOI': '10.1186/s13063-022-06375-w', 'article-title': 'The efficacy of curcumin-piperine co-supplementation on clinical ' 'symptoms, duration, severity, and inflammatory factors in COVID-19 ' 'outpatients: a randomized double-blind, placebo-controlled trial', 'volume': '23', 'author': 'Askari', 'year': '2022', 'journal-title': 'Trials'}, { 'key': '2023092304121090100_ciad187-B34', 'doi-asserted-by': 'crossref', 'DOI': '10.1126/scitranslmed.aal3920', 'article-title': 'Leukotriene B4 antagonism ameliorates experimental lymphedema', 'volume': '9', 'author': 'Tian', 'year': '2017', 'journal-title': 'Sci Transl Med'}, { 'key': '2023092304121090100_ciad187-B35', 'doi-asserted-by': 'crossref', 'first-page': '1637', 'DOI': '10.1016/S0140-6736(21)00676-0', 'article-title': 'Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): ' 'a randomised, controlled, open-label, platform trial', 'volume': '397', 'author': 'RECOVERY Collaborative Group', 'year': '2021', 'journal-title': 'Lancet'}, { 'key': '2023092304121090100_ciad187-B36', 'doi-asserted-by': 'crossref', 'first-page': '1491', 'DOI': '10.1056/NEJMoa2100433', 'article-title': 'Interleukin-6 receptor antagonists in critically ill patients with ' 'Covid-19', 'volume': '384', 'author': 'REMAP-CAP Investigators', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': '2023092304121090100_ciad187-B37', 'doi-asserted-by': 'crossref', 'first-page': '795', 'DOI': '10.1056/NEJMoa2031994', 'article-title': 'Baricitinib plus remdesivir for hospitalized adults with Covid-19', 'volume': '384', 'author': 'Kalil', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': '2023092304121090100_ciad187-B38', 'doi-asserted-by': 'crossref', 'first-page': '1401', 'DOI': '10.7326/M22-0924', 'article-title': 'The association of baseline plasma SARS-CoV-2 nucleocapsid antigen ' 'level and outcomes in patients hospitalized with COVID-19', 'volume': '175', 'author': 'ACTIV-3/TICO Study Group', 'year': '2022', 'journal-title': 'Ann Intern Med'}], 'container-title': 'Clinical Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciad187/50310958/ciad187.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/cid/article-pdf/77/2/186/51728055/ciad187.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/cid/article-pdf/77/2/186/51728055/ciad187.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 9, 23]], 'date-time': '2023-09-23T04:12:58Z', 'timestamp': 1695442378000}, 'score': 1, 'resource': {'primary': {'URL': 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