A Phase I, Double-blind, Randomized, Placebo Controlled, Dose Escalation Study of Valortim® (MDX-1303) Administered Intravenously (IV) as a 120 Minute Infusion in Healthy, Normal Subjects

Valortim is the name of the experimental drug that volunteers will receive in this study. Valortim may also be called MDX-1303. Experimental means that the drug is not yet approved by the Food and Drug Administration (FDA). Valortim is a monoclonal antibody (laboratory-made immune system molecule) for the treatment of inhalation anthrax (when the infection starts in the lungs). Valortim works by attaching itself to part of the anthrax toxin preventing the toxin from doing damage to cells. This study is being conducted to see if Valortim given over 120 minutes is safe and tolerable. This study will take place in five parts: Screening Phase, Check-in Phase (the day you arrive at Quintiles to start the study), Treatment Phase (the time when you receive the study medication), Follow-up Phase (the time after you receive the study medication) and Final Visit.

开始日期2010-12-01

申办/合作机构

PharmAthene, Inc.

[+3]

NCT01204866 / Completed临床1期

A Phase I, Open Label, Controlled Study of Valortim® (MDX-1303) and Its Selected Formulation Components When Introduced Percutaneously in Subjects Who Have and Have Not Been Exposed to Valortim Administered Intravenously

The purpose of this study is to determine if Valortim, or one or more of its selected formulation components, induces a wheal reaction when introduced percutaneously.
Two of 4 subjects dosed in a previous study with a modified formulation of Valortim experienced treatment related adverse events which were suggestive of allergic or allergic-like reactions. In order to better characterize these reactions and determine if they represent allergic or allergic-like reactions to Valortim or one or more of its components, skin testing of Valortim and selected components on naïve and Valortim-exposed subjects will be performed in this study

开始日期2010-07-01

申办/合作机构

PharmAthene, Inc.

[+2]

NCT00964561 / Suspended临床1期

A Phase I, Single Blind, Randomized, Placebo Controlled, Drug Interaction Study of Intravenous (IV) Valortim® and Intravenous (IV) Ciprofloxacin in Healthy, Normal Subjects

The purpose of this study is to evaluate the safety and tolerability of short-term dosing of IV ciprofloxacin when administered concomitantly with IV Valortim in healthy normal human subjects.

开始日期2009-08-01

申办/合作机构

PharmAthene, Inc.

[+4]

100 项与 MDX-1303 相关的临床结果

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100 项与 MDX-1303 相关的转化医学

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100 项与 MDX-1303 相关的专利（医药）

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项与 MDX-1303 相关的文献（医药）

2020-01-15·International journal of cancer

A novel, safe, fast and efficient treatment for Her2‐positive and negative bladder cancer utilizing an EGF‐anthrax toxin chimera

Article

作者: Elzey, Bennett D. ; Knapp, Deborah W. ; Madhivanan, Kayalvizhi ; Rabideau, Amy ; Subramanian, Sneha ; Edwards, Daniel F. ; Santos, Michael ; Koch, Michael ; Ramadesikan, Swetha ; Aguilar, Ruben C. ; Dhawan, Deepika ; Collier, John ; Kischuk, Erin M. ; Ratliff, Timothy L. ; Jack, Sherwin ; Pentelute, Bradley ; Kaimakliotis, Hristos ; McCluskey, Andrew ; Loftis, Alexander R. ; Truex, Nicholas ; Lu, Mike

Bladder cancer is the sixth most common cancer in the United States, and it exhibits an alarming 70% recurrence rate. Thus, the development of more efficient antibladder cancer approaches is a high priority. Accordingly, this work provides the basis for a transformative anticancer strategy that takes advantage of the unique characteristics of the bladder. Unlike mucin‐shielded normal bladder cells, cancer cells are exposed to the bladder lumen and overexpress EGFR. Therefore, we used an EGF‐conjugated anthrax toxin that after targeting EGFR was internalized and triggered apoptosis in exposed bladder cancer cells. This unique agent presented advantages over other EGF‐based technologies and other toxin‐derivatives. In contrast to known agents, this EGF‐toxin conjugate promoted its own uptake via receptor microclustering even in the presence of Her2 and induced cell death with a LC50 < 1 nM. Furthermore, our data showed that exposures as short as ≈3 min were enough to commit human (T24), mouse (MB49) and canine (primary) bladder cancer cells to apoptosis. Exposure of tumor‐free mice and dogs with the agent resulted in no toxicity. In addition, the EGF‐toxin was able to eliminate cells from human patient tumor samples. Importantly, the administration of EGF‐toxin to dogs with spontaneous bladder cancer, who had failed or were not eligible for other therapies, resulted in ~30% average tumor reduction after one treatment cycle. Because of its in vitro and in vivo high efficiency, fast action (reducing treatment time from hours to minutes) and safety, we propose that this EGF–anthrax toxin conjugate provides the basis for new, transformative approaches against bladder cancer.

2019-12-01·BMC infectious diseases3区 · 医学

Different mechanisms of two anti-anthrax protective antigen antibodies and function comparison between them

3区 · 医学

ArticleOA

作者: Cao, Yongping ; Zhou, Tingting ; Feng, Zhengqin ; Tang, Qi ; Xiong, Siping ; Wang, Chunhui ; Zhu, Jin ; Zheng, Feng ; Liang, Xudong

Abstract:

Background:

Bacillus anthracis causes a highly lethal infectious disease primarily due to toxin-mediated injury. Antibiotics are no longer effective to treat the accumulation of anthrax toxin, thereby new strategies of antibody treatment are essential. Two anti- anthrax protective antigen (PA) antibodies, hmPA6 and PA21, have been reported by our lab previously.

Methods:

The mechanisms of the two antibodies were elucidated by Electrophoresis, Competitive Enzyme-linked immune sorbent assay, Western blot analysis and immunoprecipitation test, and in vitro, in vivo (F344 rats) treatment test. The epitopes of the two antibodies were proved by Western blot and Enzyme-linked immune sorbent assay with different domains of PA.

Results:

In this study, we compared affinity and neutralization of these two antibodies. PA21 was better in protecting cells and rats, whereas hmPA6 had higher affinity. Furthermore, the neutralization mechanisms of the two antibodies and their recognition domains of PA were studied. The results showed that hmPA6 recognized domain IV, thus PA could not bind to cell receptors. Conversely, PA21 recognized domain II, thereby limiting heptamer oligomerization of PA63 in cells.

Conclusions:

Our studies elucidated the mechanisms and epitopes of hmPA6 and PA21. The present investigation can advance future use of the two antibodies in anthrax treatment or prophylaxis, and potentially as a combination treatment as the antibodies target different epitopes.

2016-11-25·Sheng wu gong cheng xue bao = Chinese journal of biotechnology

[Screening of full human anthrax lethal factor neutralizing antibody in transgenic mice].

Article

作者: Yu, Changming ; Liu, Kun ; Liu, Shuling ; Wang, Xiaolin ; Liu, Weicen ; Song, Xiaohong ; Zhang, Jun ; Chi, Xiangyang ; Liu, Ju ; Wen, Zhonghua ; Qiu, Shunfang ; Fan, Pengfei ; Fu, Ling

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

项与 MDX-1303 相关的新闻（医药）

2011-06-27

·BioSpace

PharmAthene, Inc. Achieves Anthrax Vaccine Program Milestone and Successfully Completes Technology Transfer

ANNAPOLIS, Md., June 27, 2011 /PRNewswire/ -- PharmAthene, Inc. (NYSE Amex: PIP) announced today that it has achieved an important technical milestone in its recombinant protective antigen (rPA) anthrax vaccine program. PharmAthene has successfully completed initial technology transfer of its manufacturing process for the bulk drug substance of its vaccine candidate, SparVax, at the 100 liter scale to a US-based manufacturing facility at Diosynth RTP. Activities to scale-up production to the final commercial 1,500 liter scale are underway. "Completion of the technology transfer for SparVax to a domestic manufacturer represents a major technical milestone and significant achievement for our program," remarked Dr. Tom Fuerst, Executive Vice President and Chief Scientific Officer. "As part of this transition, our process sciences team was able to optimize the production process for SparVax increasing our bulk drug substance production yield approximately six-fold, further improving the cost effectiveness of our anthrax vaccine for the United States government. We are currently moving forward to complete the implementation of the GMP manufacturing processes and look forward to commencing additional clinical and non-clinical studies of SparVax in the coming months. Importantly, our achievement of this milestone will enable us to pursue additional advanced development funding." Dr. Fuerst continued, "The benefits of rPA-based vaccines are well established, and we believe our program is at the forefront of efforts in this field. Most importantly, our rPA anthrax vaccine program meets a fundamental objective of Project BioShield, which was established to encourage the development and acquisition of newer, modern medical countermeasures that offer potential improvements in cost, convenience, safety and effectiveness for the U.S. government and its citizens." PharmAthene's rPA anthrax vaccine program has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health and the Biomedical Advanced Research and Development Authority. About PharmAthene, Inc. PharmAthene was formed to meet the critical needs of the United States and its allies by developing and commercializing medical countermeasures against biological and chemical weapons. PharmAthene's lead product development programs include: SparVax second generation recombinant protective antigen (rPA) anthrax vaccine Valortim® fully human monoclonal antibody for the prevention and treatment of anthrax infection rBChE (recombinant butyrylcholinesterase) a medical countermeasure for nerve agent poisoning by organophosphorous compounds, including nerve agents and pesticides Statement on Cautionary Factors Except for the historical information presented herein, matters discussed may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words "potential"; "believe"; "anticipate"; "intend"; "plan"; "expect"; "estimate"; "could"; "may"; "should"; "will"; "project"; "potential"; or similar statements are forward-looking statements. PharmAthene disclaims any intent or obligation to update these forward-looking statements other than as required by law. Risks and uncertainties include risk associated with the reliability of the results of the studies relating to human safety and possible adverse effects resulting from the administration of the Company's product candidates, unexpected funding delays and/or reductions or elimination of U.S. government funding for one or more of the Company's development programs, the award of government contracts to our competitors, unforeseen safety issues, challenges related to the development, scale-up, technology transfer, and/or process validation of manufacturing processes for our product candidates, unexpected determinations that these product candidates prove not to be effective and/or capable of being marketed as products, challenges related to the implementation of our NYSE Amex compliance plan, as well as risks detailed from time to time in PharmAthene's Forms 10-K and 10-Q under the caption "Risk Factors" and in its other reports filed with the U.S. Securities and Exchange Commission (the "SEC"). In particular, at this point there can be no assurance that PharmAthene's rPA product candidate will be shown to be safe and effective and approved by regulatory authorities for use in humans. Copies of PharmAthene's public disclosure filings are available from its investor relations department and our website under the investor relations tab at . SOURCE PharmAthene, Inc.

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100 项与 MDX-1303 相关的药物交易

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