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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAmong the strategies being explored to prevent infection with human immunodeficiency virus type 1 is ibalizumab, a humanized monoclonal antibody that binds to CD4 domain 2 and blocks the entry of HIV-1 into CD4-positive T cells. This article discusses the Safety Study of Ibalizumab Subcutaneous Injection in Healthy Volunteers (TMB-108) [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01292174\u0026amp;atom=%2Fspmdc%2F14%2F28%2F9.atom\u0022\u003ENCT01292174\u003C\/a\u003E] results of a study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous injections of ibalizumab.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHIV \u0026amp; AIDS\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAmong the strategies being explored to prevent infection with human immunodeficiency virus type 1 (HIV-1) is ibalizumab, a humanized monoclonal antibody that binds to CD4 domain 2 and blocks the entry of HIV-1 into CD4-positive T cells. Steven Weinheimer, PhD, TaiMed Biologics, Irvine, California, USA, presented the results of a study of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of subcutaneous (SC) injections of ibalizumab.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ESafety Study of Ibalizumab Subcutaneous Injection in Healthy Volunteers (TMB-108) [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01292174\u0026amp;atom=%2Fspmdc%2F14%2F28%2F9.atom\u0022\u003ENCT01292174\u003C\/a\u003E] was a double-blind, placebo-controlled study that randomly assigned 8 participants at risk for acquiring HIV to each of 3 sequential escalating dose cohorts. Of the 24 participants enrolled, 89% were men; 65% were white; 23% were black; the mean age was 30 years; and the mean weight was 82 kg. Participants received 4 weekly SC injections of ibalizumab (120, 240, and 480 mg) or placebo. Follow-up continued for 26 weeks following dosing, and assessments included safety, PK, CD4 receptor occupancy, CD4 receptor density, and a CD4-dependent antibody response to hepatitis A virus (HAV) following challenge with HAV antigen at weeks 1 and 25.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThere were no serious adverse events (AEs) and no discontinuations due to AEs. Treatment-related AEs occurred in 2 (28.6%) participants in the placebo group and 6 (31.6%) in the ibalizumab treatment groups (n = 4 of 7 in the 240-mg group; n = 2 of 6 in the 480-mg group). The most frequently reported treatment-emergent AEs were headache, upper respiratory tract infection, oropharyngeal pain and cough, and pruritus. No injection site reactions or anti-ibalizumab antibodies were observed, nor clinically significant changes in laboratory parameters, dose-response and temporal trends in vital signs, or physical examinations.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EDaily serum ibalizumab concentrations after the first and fourth doses exhibited nonlinear PK consistent with target-mediated drug disposition, as shown in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E. Higher first doses were associated with slower elimination, delayed absorption, and disproportionately higher systemic exposure.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/28\/9\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Ibalizumab Mean Serum Concentrations\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1263345191\u0022 data-figure-caption=\u0022Ibalizumab Mean Serum Concentrations\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/28\/9\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/28\/9\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/28\/9\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11858\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EIbalizumab Mean Serum Concentrations\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from S Weinheimer, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EMaximum and trough serum concentrations and the area under the concentration-time curve increased with repeat doses. Results from 3 participants with body weights \u0026gt; 100 kg suggest that SC fat might delay the absorption of ibalizumab. All participants who received the highest dose had detectable levels of ibalizumab in their semen.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ENo participants had significant changes from baseline in CD4-positive T-cell counts. Anti-HAV antibodies were measured at weeks 5 and 29; antibody responses were detected in 100% of participants receiving placebo and in 53% and 94% receiving ibalizumab at these time points, respectively. The target for antiviral suppression is at least 85% CD4 receptor occupancy, which was achieved for 3 to 4 days after the first dose and for 6 to 7 days after the fourth dose of the 2 lower doses; nearly 100% receptor occupancy occurred for the entire dosing period for the highest dose.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAlthough the results suggest that SC ibalizumab may have the potential to prevent HIV-1 infection, the effects on antibody response to HAV antigen challenge require further study.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/28\/9.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm0z2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm0z2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}