Phase 2 Clinical Trial of Coralmyn for Coral Snake Bite (BB-IND 13926,01/02/09)

University Of Arizona, Tucson AZ

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Abstract

Abstract Background: Each year, poison control centers report approximately 75 bites by coral snakes (Micrurus and Micruroides species) in the United States. More than half of these occur in Florida, with the rest concentrated in the southeastern states, westward as far as Texas. Before the introduction of anti-coral antivenom by Wyeth in 1967, approximately 10% of Micrurus bites were potentially fatal, due to ventilatory failure caused by neurotoxins active at the neuromuscular junction. Wyeth Ayerst has recently ceased production of this antivenom. In October of 2009, the last vials will expire, leaving the U.S. without a licensed supplier of antivenom. Objectives: Licensure of a new antivenom product, Coralmyn. Specific Aims: (1) Demonstrate the safety of Coralmyn in patients bitten by Micrurus coral snakes, by monitoring recipients for Type I and Type III immune reactions. (2) Demonstrate the value of plasma venom levels as a surrogate endpoint in coral snake bites by relating venom levels to severity of envenomation, before and after treatment. (3) Demonstrate that cost of treatment is different for patients presenting to hospitals with and without antivenom in stock, and use patient cost data to complete a pharmacoeconomic model comparing distribution methodologies applicable to Phase 3 or 4 study design. Research Design and Methods: This will be an open-label Phase 2 clinical trial of Coralmyn (anti-coral serum injectable solution, Instituto Bioclon, S.A. de C.V.) in male and female human patients of any age who present for emergency care following bites by coral snakes of genus Micrurus. Using grant funds, as many hospitals as economically feasible (at least 3 in Florida) will be provided with antivenom with which to enroll patients promptly in the study, using a central IRB. Patients presenting to other sites may enroll in the study either by interhospital transfer or by emergency delivery of antivenom to out-of-network hospitals. In all cases, clinical observations and plasma for venom levels will be collected at study enrollment and hourly until start of study drug. Following infusion of antivenom, clinical observations and plasma collection will be repeated at intervals until hospital discharge; and telephone follow-up will continue through day 22. Clinical and financial data will be extracted by examination of patient records including standardized data collection sheets completed prospectively by hospital staff and extracted into Case Report Forms secondarily by study staff at a central site. Plasma will be frozen and held for batch analysis every six months, using a Micrurus-specific ELISA assay. Statistical analysis of safety indicators will be conducted using Cox Proportional Hazard or survival models. Venom levels will be analyzed using a combination of logistic regression and ANOVA and compared with neurological assessments using a Generalized Linear Mixed Model. Cost data will be entered into a decision-tree model constructed in TreeAge HealthcarePro, and sensitivity analysis will be performed using MonteCarlo simulation.