{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T16:51:50Z","timestamp":1758905510236},"reference-count":18,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            MDX-1303 (Valortim) is a fully human monoclonal antibody (hMAb) with a high affinity for\n            <jats:named-content content-type=\"genus-species\">Bacillus anthracis<\/jats:named-content>\n            protective antigen (PA). MDX-1303 binds to PA and interferes with the activity of the anthrax toxin; it was selected based on its superior functional activity in the toxin neutralization activity (TNA) assay. MDX-1303 has demonstrated efficacy in the postexposure and therapeutic settings in New Zealand White rabbits, cynomolgus monkeys, and African green monkeys. This phase I study sought to characterize the safety, tolerability, immunogenicity, and pharmacokinetics (PK)\/pharmacodynamics (PD) of MDX-1303 in healthy human subjects. Cohorts of 3 to 10 subjects were administered MDX-1303 as either a single intravenous (i.v.) dose at dose levels of 0.3, 1, 3, 10, and 20 mg\/kg of body weight or as a single intramuscular (i.m.) dose at 100 mg. Forty-six subjects were enrolled, and 16 (35%) of these subjects experienced one or more grade 1 adverse events considered to be related to treatment with MDX-1303. There were no grade 2 to 4 adverse events or serious adverse events (SAEs) considered to be related to treatment. The mean half-life of MDX-1303 ranged from 22 to 33 days across the i.v. administration cohorts and was approximately 32 days following i.m. administration. Systemic exposure following 100-mg i.m. administration was within the range of exposure following 1-mg\/kg i.v. administration with a relative bioavailability of approximately 65%. MDX-1303 was generally well tolerated, and no anti-MDX-1303 antibodies were detected following a single dose.\n          <\/jats:p>","DOI":"10.1128\/cvi.05059-11","type":"journal-article","created":{"date-parts":[[2011,10,6]],"date-time":"2011-10-06T06:07:38Z","timestamp":1317881258000},"page":"2136-2142","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Phase I Study Evaluating the Safety and Pharmacokinetics of MDX-1303, a Fully Human Monoclonal Antibody against Bacillus anthracis Protective Antigen, in Healthy Volunteers"],"prefix":"10.1128","volume":"18","author":[{"given":"Valerie","family":"Riddle","sequence":"first","affiliation":[{"name":"PharmAthene, Inc., Annapolis, Maryland 21401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Leese","sequence":"additional","affiliation":[{"name":"Quintiles Phase I Services, Lenexa, Kansas 66215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diann","family":"Blanset","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Princeton, New Jersey 08540"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melany","family":"Adamcio","sequence":"additional","affiliation":[{"name":"PharmAthene, Inc., Annapolis, Maryland 21401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Meldorf","sequence":"additional","affiliation":[{"name":"PharmAthene, Inc., Annapolis, Maryland 21401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Lowy","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company, Princeton, New Jersey 08540"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1073\/pnas.90.6.2291","article-title":"Pathology of inhalational anthrax in 42 cases from the Sverdlosk outbreak of 1979","volume":"90","author":"Abramova F. A.","year":"1993","unstructured":"AbramovaF. A. GrinbergL. M. YampolskayaO. V. WalkerD. H.. 1993. Pathology of inhalational anthrax in 42 cases from the Sverdlosk outbreak of 1979. Proc. Natl. Acad. Sci. U. S. A. 90:2291\u20132294.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1001\/jama.1997.03550050074036","article-title":"Biological warfare: a historical perspective","volume":"278","author":"Christopher G. W.","year":"1997","unstructured":"ChristopherG. W. CieslakJ. PavlinJ. A. EitzenE. M.Jr. 1997. Biological warfare: a historical perspective. JAMA 278:412\u2013417.","journal-title":"JAMA"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1017\/S0317167100047697","article-title":"Impact of migraine and tension-type headache on lifestyle, consulting behavior, and medication use: a Canadian population survey","volume":"20","author":"Edmeads J.","year":"1993","unstructured":"EdmeadsJ.. 1993. Impact of migraine and tension-type headache on lifestyle, consulting behavior, and medication use: a Canadian population survey. Can. J. Neurol. Sci. 20:131\u2013137.","journal-title":"Can. J. Neurol. Sci."},{"key":"e_1_3_2_6_2","unstructured":"Executive Action LLC. 2007. Spores: the threat of a catastrophic anthrax attack on America. Signature Book Printing Gaithersburg MD."},{"key":"e_1_3_2_7_2","unstructured":"FDA. 2009. Draft guidance for industry: animal models\u2014essential elements to address efficacy under the Animal Rule. http:\/\/www.fda.gov\/cder\/guidance\/index.htm. Accessed 31 March 2009."},{"key":"e_1_3_2_8_2","first-page":"335","article-title":"Anthrax: clinical features, pathogenesis, and potential biological warfare threat","volume":"20","author":"Friedlander A. M.","year":"2000","unstructured":"FriedlanderA. M. 2000. Anthrax: clinical features, pathogenesis, and potential biological warfare threat. Curr. Clin. Top. Infect. Dis. 20:335\u2013349.","journal-title":"Curr. Clin. Top. Infect. Dis."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1097\/00006254-198611000-00024","article-title":"Older maternal age and pregnancy outcome: a review of the literature","volume":"41","author":"Hansen J.","year":"1986","unstructured":"HansenJ. 1986. Older maternal age and pregnancy outcome: a review of the literature. Obstet. Gynecol. Surv. 41:726\u2013742.","journal-title":"Obstet. Gynecol. Surv."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1001\/jama.281.18.1735","article-title":"Anthrax as a biological weapon: medical and public health management","volume":"281","author":"Inglesby T. V.","year":"1999","unstructured":"InglesbyT. V.. 1999. Anthrax as a biological weapon: medical and public health management. JAMA 281:1735\u20131745.","journal-title":"JAMA"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2236"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0706.010604"},{"key":"e_1_3_2_13_2","first-page":"1887","volume-title":"Principles and practice of infectious diseases","author":"Mandell G. L.","year":"2000","unstructured":"MandellG. L. BennetJ. E. DolinR. (ed.). 2000. Principles and practice of infectious diseases, 5th ed., p. 1887\u20131888. Churchill-Livingstone, New York, NY.","edition":"5"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/0895-4356(91)90147-2","article-title":"Epidemiology of headache in a general population: a prevalence study","volume":"44","author":"Rasmussen B. K.","year":"1991","unstructured":"RasmussenB. K. JensenR. SchrollM. OlesenJ.. 1991. Epidemiology of headache in a general population: a prevalence study. J. Clin. Epidemiol. 44:1147\u20131157.","journal-title":"J. Clin. Epidemiol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1056\/NEJMra012892","article-title":"Recognition and management of anthrax\u2014an update","volume":"345","author":"Swartz M. N.","year":"2001","unstructured":"SwartzM. N. 2001. Recognition and management of anthrax\u2014an update. N. Engl. J. Med. 345:1621\u20131626.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1525-1497.2005.0094.x","article-title":"Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels","volume":"20","author":"Thavendiranathan P.","year":"2005","unstructured":"ThavendiranathanP. BagaiA. EbidiaA. DetskyA. S. ChoudhryN. K.. 2005. Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J. Gen. Intern. Med. 20:520\u2013524.","journal-title":"J. Gen. Intern. Med."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1086\/377738","article-title":"Serious adverse events among participants in the Centers for Disease Control and Prevention's anthrax vaccine and antimicrobial availability program for persons at risk for bioterrorism-related inhalational anthrax","volume":"37","author":"Tierney B.","year":"2003","unstructured":"TierneyB.. 2003. Serious adverse events among participants in the Centers for Disease Control and Prevention's anthrax vaccine and antimicrobial availability program for persons at risk for bioterrorism-related inhalational anthrax. Clin. Infect. Dis. 37:905\u2013911.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00712-06"},{"key":"e_1_3_2_19_2","first-page":"26","article-title":"Attacking anthrax","author":"Young J. T.","year":"2003","unstructured":"YoungJ. T. CollierR. J.. November 2003. Attacking anthrax. Scientific American Exclusive Online Issue, p. 26\u201332.","journal-title":"Scientific American Exclusive Online Issue"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.05059-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.05059-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:44:21Z","timestamp":1627591461000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.05059-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12]]},"references-count":18,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["10.1128\/CVI.05059-11"],"URL":"https:\/\/doi.org\/10.1128\/cvi.05059-11","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12]]},"assertion":[{"value":"2011-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-09-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}