A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating Pharmacokinetics and Safety of a Human Monoclonal Antibody (AVP-21D9) in Normal Healthy Volunteers

Primary:
• To compare the safety profile of a single intravenous administration of AVP-21D9 as compared with Placebo
Secondary:
To evaluate the pharmacokinetics (PK) of a single intravenous administration of AVP-21D9
To evaluate the immunogenicity of AVP-21D9

开始日期2010-08-01

申办/合作机构

Emergent BioSolutions, Inc.

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100 项与 AVP-21D9 相关的临床结果

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100 项与 AVP-21D9 相关的转化医学

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100 项与 AVP-21D9 相关的专利（医药）

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项与 AVP-21D9 相关的文献（医药）

2014-07-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Efficacy and Safety of AVP-21D9, an Anthrax Monoclonal Antibody, in Animal Models and Humans

2区 · 医学

Article

作者: Skiadopoulos, Mario H. ; Ionin, Boris ; Bernton, Edward ; Malkevich, Nina V. ; Meister, Gabriel T. ; Hopkins, Robert J. ; Vela, Eric M. ; Nabors, Gary S. ; Atiee, George ; Aimes, Ronald T. ; Johnson, Virginia

ABSTRACT Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis . Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis -infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration ( Cmax ) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.)

2007-07-01·Infection and Immunity2区 · 医学

Human Monoclonal Antibody AVP-21D9 to Protective Antigen Reduces Dissemination of the Bacillus anthracis Ames Strain from the Lungs in a Rabbit Model

2区 · 医学

Article

作者: Taormina, Joanna ; Chatuev, Bagram M. ; Sower, Laurie ; Pawlik, Jennifer ; Wenglikowski, Autumn ; Stanberry, Lawrence R. ; Sircar, Jagadish ; Comer, Jason E. ; Chopra, Ashok K. ; Bush, Kathryn ; Scholz, Wolfgang W. ; Peterson, Johnny W. ; Hardcastle, Jason ; Thomas, John ; Noffsinger, David M. ; Baze, Wallace B. ; Moen, Scott ; Walberg, Kristin G. ; Sawada, Ritsuko

ABSTRACT Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some naïve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.

2006-02-01·Infection and Immunity2区 · 医学

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

2区 · 医学

Article

作者: Noffsinger, David M. ; Kang, Angray S. ; Peterson, Johnny W. ; Walberg, Kristin G. ; Comer, Jason E. ; Chopra, Ashok K. ; Wenglikowski, Autumn ; Chatuev, Bagram M. ; Scholz, Wolfgang W. ; Stanberry, Lawrence R. ; Sircar, Jagadish

ABSTRACT Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD 50 s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD 50 s of B. anthracis Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for prophylaxis or treatment following inhalation anthrax infection.

100 项与 AVP-21D9 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
炭疽	临床1期	-	Avanir Pharmaceuticals, Inc.	-
葡萄球菌感染	临床1期	美国	Avanir Pharmaceuticals, Inc.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01202695 (Pubmed \| Antimicrob Agents Chemother)	临床1期	炭疽	50	AVP-21D9	鹹構鹹製壓艱襯鏇繭餘(構積壓襯鹽積廠鏇鹹構) = 願繭鹽製糧醖衊積鏇襯艱範淵醖鬱築壓襯製積 (獵齋窪願鬱鹹憲鏇鏇艱 )	-	2014-07-01