{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:21:29Z","timestamp":1772245289878,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Shiga toxin\u2010producing <jats:styled-content style=\"fixed-case\"><jats:italic>Escherichia coli<\/jats:italic><\/jats:styled-content>\u2010haemolytic uraemic syndrome (STEC\u2010HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab\u2032)<jats:sub>2<\/jats:sub> fragments from equine immunoglobulins, neutralizes Stx1\/Stx2, potentially preventing the onset of HUS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single\u2010centre, randomized, phase 1, single\u2010blind, placebo\u2010controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (<jats:italic>n<\/jats:italic>\u2009=\u20094) to receive a single INM004 dose of 2 or 4\u2009mg kg<jats:sup>\u22121<\/jats:sup>, or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4\u00a0mg kg<jats:sup>\u22121<\/jats:sup> repeated every 24\u2009h, or placebo (INM004:placebo ratio of 5:1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight subjects (57.1%) experienced mild treatment\u2010emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24\u2009h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2\u00a0h after infusion, with median <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> values of 45.1 and 77.7\u00a0\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup> for 2 and 4\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup>, respectively. The serum concentration of INM004 declined in a biphasic manner (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub> range 30.7\u201352.9\u00a0h). Systemic exposures increased with each subsequent dose in a dose\u2010proportional manner, exhibiting accumulation. Geometric median <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and <jats:italic>AUC<\/jats:italic> values were 149 and 10\u2009300\u2009\u03bcg\u2009h\u2009mL<jats:sup>\u22121<\/jats:sup>, respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2\u00a0mg\u2009kg<jats:sup>\u22121<\/jats:sup> showed neutralizing capacity against Stx1 and Stx2 in in vitro assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results obtained in this first\u2010in\u2010human study support progression into the phase 2 trial in children with HUS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15999","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T11:05:00Z","timestamp":1706612700000},"page":"1142-1151","source":"Crossref","is-referenced-by-count":8,"title":["A phase I study to evaluate the safety, tolerance and pharmacokinetics of anti\u2010Shiga toxin hyperimmune equine F (ab\u2032)<sub>2<\/sub> fragments in healthy volunteers"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-4677","authenticated-orcid":false,"given":"Yanina","family":"Hiriart","sequence":"first","affiliation":[{"name":"National Scientific and Technological Research Council, CONICET  Godoy Cruz 2290 (C1425FQB) CABA Buenos Aires Argentina"},{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Scibona","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Section Hospital Italiano de Buenos Aires  Tte. Gral. Juan Domingo Per\u00f3n 4190, CP (C1181ACH), CABA Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Ferraris","sequence":"additional","affiliation":[{"name":"Internal Medicine Section Hospital Italiano de Buenos Aires  Tte. Gral. Juan Domingo Per\u00f3n 4190, CP (C1181ACH), CABA Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldo H.","family":"Belloso","sequence":"additional","affiliation":[{"name":"Terra Nova Innovation Unit Hospital Italiano de Buenos Aires  Tte. Gral. Juan Domingo Per\u00f3n 4190, CP (C1181ACH) CABA Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Beruto","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Section Hospital Italiano de Buenos Aires  Tte. Gral. Juan Domingo Per\u00f3n 4190, CP (C1181ACH), CABA Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-247X","authenticated-orcid":false,"given":"Facundo","family":"Garcia Bournissen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Clinical Pharmacology, Department of Pediatrics, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanesa","family":"Zylberman","sequence":"additional","affiliation":[{"name":"National Scientific and Technological Research Council, CONICET  Godoy Cruz 2290 (C1425FQB) CABA Buenos Aires Argentina"},{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Goldbaum","sequence":"additional","affiliation":[{"name":"National Scientific and Technological Research Council, CONICET  Godoy Cruz 2290 (C1425FQB) CABA Buenos Aires Argentina"},{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"},{"name":"CRIP, Centro de redise\u00f1o e ingenier\u00eda de prote\u00ednas  25 de Mayo y Francia (CP 1650) San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linus","family":"Spatz","sequence":"additional","affiliation":[{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Colonna","sequence":"additional","affiliation":[{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Sanguineti","sequence":"additional","affiliation":[{"name":"Inmunova SA  Av. 25 de Mayo 1021 (CP1650), San Mart\u00edn Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ventura A.","family":"Simonovich","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Section Hospital Italiano de Buenos Aires  Tte. 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