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First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers

This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measur...

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Autores principales: Stevens, Misty W, Henry, Ralph L, Owens, S Michael, Schutz, Ralph, Gentry, W Brooks
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623385/
https://www.ncbi.nlm.nih.gov/pubmed/25484042
http://dx.doi.org/10.4161/19420862.2014.976431
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author Stevens, Misty W
Henry, Ralph L
Owens, S Michael
Schutz, Ralph
Gentry, W Brooks
author_facet Stevens, Misty W
Henry, Ralph L
Owens, S Michael
Schutz, Ralph
Gentry, W Brooks
author_sort Stevens, Misty W
collection PubMed
description This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17–19 d in the 3 highest dose groups and volume of distribution of 5–6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration.
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spelling pubmed-46233852015-11-12 First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers Stevens, Misty W Henry, Ralph L Owens, S Michael Schutz, Ralph Gentry, W Brooks MAbs Reports This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17–19 d in the 3 highest dose groups and volume of distribution of 5–6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration. Taylor & Francis 2014-11-03 /pmc/articles/PMC4623385/ /pubmed/25484042 http://dx.doi.org/10.4161/19420862.2014.976431 Text en © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Reports
Stevens, Misty W
Henry, Ralph L
Owens, S Michael
Schutz, Ralph
Gentry, W Brooks
First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title_full First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title_fullStr First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title_full_unstemmed First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title_short First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
title_sort first human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623385/
https://www.ncbi.nlm.nih.gov/pubmed/25484042
http://dx.doi.org/10.4161/19420862.2014.976431
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