Kim Hanna, Maria Cristina Cruz, Elsa Mondou, Edward Corsi, Peter Vandeberg
{"title":"给予单剂量辛酸免疫球蛋白/层析纯化的健康受试者狂犬病抗体的安全性和中和性。","authors":"Kim Hanna, Maria Cristina Cruz, Elsa Mondou, Edward Corsi, Peter Vandeberg","doi":"10.2147/CPAA.S166454","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rabies immune globulin (RIG) and vaccination series are necessary for postexposure prophylaxis. A new formulation of RIG (human) purified by caprylate/chromatography (RIG-C) was evaluated.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT02139657.</p><p><strong>Materials and methods: </strong>This open-label, single-arm study in healthy subjects evaluated neutralizing rabies antibody concentrations produced from a single 20 IU/kg intramuscular (IM) dose of RIG-C as measured by rapid fluorescent focus inhibition test (50% neutralization endpoint) 1-hour postdose and on days 1, 2, 4, 6, 8, 10, 14, 18, and 21.</p><p><strong>Results: </strong>Twelve subjects were enrolled into the study. No discontinuations, serious adverse events (AEs), or treatment-emergent clinically significant changes in laboratory parameters were observed. All AEs resolved and were mild except 1 moderate AE of oropharyngeal pain. Injection site pain (4 subjects) was most commonly reported. RIG-C produced a rapid increase in neutralizing rabies antibody: mean value 0.113 IU/mL at 24 hours after IM injection, peak on day 4 (0.132 IU/mL), persisting through day 21 (0.116 IU/mL). The mean reciprocal titer was 11.5 by day 2; the peak value of 12.1 was achieved on day 4; and a mean value ≥10.6 was maintained through day 21.</p><p><strong>Conclusion: </strong>RIG-C was well tolerated and provided neutralizing rabies antibodies, which combined with vaccine series after rabies exposure, should result in effective prophylaxis per World Health Organization/Centers for Disease Control and Prevention guidelines.</p>","PeriodicalId":10406,"journal":{"name":"Clinical Pharmacology : Advances and Applications","volume":"10 ","pages":"79-88"},"PeriodicalIF":3.1000,"publicationDate":"2018-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/CPAA.S166454","citationCount":"6","resultStr":"{\"title\":\"Safety and neutralizing rabies antibody in healthy subjects given a single dose of rabies immune globulin caprylate/chromatography purified.\",\"authors\":\"Kim Hanna, Maria Cristina Cruz, Elsa Mondou, Edward Corsi, Peter Vandeberg\",\"doi\":\"10.2147/CPAA.S166454\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Rabies immune globulin (RIG) and vaccination series are necessary for postexposure prophylaxis. A new formulation of RIG (human) purified by caprylate/chromatography (RIG-C) was evaluated.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT02139657.</p><p><strong>Materials and methods: </strong>This open-label, single-arm study in healthy subjects evaluated neutralizing rabies antibody concentrations produced from a single 20 IU/kg intramuscular (IM) dose of RIG-C as measured by rapid fluorescent focus inhibition test (50% neutralization endpoint) 1-hour postdose and on days 1, 2, 4, 6, 8, 10, 14, 18, and 21.</p><p><strong>Results: </strong>Twelve subjects were enrolled into the study. No discontinuations, serious adverse events (AEs), or treatment-emergent clinically significant changes in laboratory parameters were observed. All AEs resolved and were mild except 1 moderate AE of oropharyngeal pain. Injection site pain (4 subjects) was most commonly reported. RIG-C produced a rapid increase in neutralizing rabies antibody: mean value 0.113 IU/mL at 24 hours after IM injection, peak on day 4 (0.132 IU/mL), persisting through day 21 (0.116 IU/mL). The mean reciprocal titer was 11.5 by day 2; the peak value of 12.1 was achieved on day 4; and a mean value ≥10.6 was maintained through day 21.</p><p><strong>Conclusion: </strong>RIG-C was well tolerated and provided neutralizing rabies antibodies, which combined with vaccine series after rabies exposure, should result in effective prophylaxis per World Health Organization/Centers for Disease Control and Prevention guidelines.</p>\",\"PeriodicalId\":10406,\"journal\":{\"name\":\"Clinical Pharmacology : Advances and Applications\",\"volume\":\"10 \",\"pages\":\"79-88\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2018-06-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2147/CPAA.S166454\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacology : Advances and Applications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/CPAA.S166454\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacology : Advances and Applications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/CPAA.S166454","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Safety and neutralizing rabies antibody in healthy subjects given a single dose of rabies immune globulin caprylate/chromatography purified.
Background: Rabies immune globulin (RIG) and vaccination series are necessary for postexposure prophylaxis. A new formulation of RIG (human) purified by caprylate/chromatography (RIG-C) was evaluated.
Materials and methods: This open-label, single-arm study in healthy subjects evaluated neutralizing rabies antibody concentrations produced from a single 20 IU/kg intramuscular (IM) dose of RIG-C as measured by rapid fluorescent focus inhibition test (50% neutralization endpoint) 1-hour postdose and on days 1, 2, 4, 6, 8, 10, 14, 18, and 21.
Results: Twelve subjects were enrolled into the study. No discontinuations, serious adverse events (AEs), or treatment-emergent clinically significant changes in laboratory parameters were observed. All AEs resolved and were mild except 1 moderate AE of oropharyngeal pain. Injection site pain (4 subjects) was most commonly reported. RIG-C produced a rapid increase in neutralizing rabies antibody: mean value 0.113 IU/mL at 24 hours after IM injection, peak on day 4 (0.132 IU/mL), persisting through day 21 (0.116 IU/mL). The mean reciprocal titer was 11.5 by day 2; the peak value of 12.1 was achieved on day 4; and a mean value ≥10.6 was maintained through day 21.
Conclusion: RIG-C was well tolerated and provided neutralizing rabies antibodies, which combined with vaccine series after rabies exposure, should result in effective prophylaxis per World Health Organization/Centers for Disease Control and Prevention guidelines.