1183. A Phase 1, Single Ascending-Dose Study of AVI-6003, a Combination of Two PMOplus Compounds with Activity against Marburg Virus
Session: Poster Abstract Session: New Approaches to Anti-Viral Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Marburg hemorrhagic fever (MHF) is a rare human disease caused by the Marburg virus (MARV), a filamentous single-stranded, negative-sense RNA virus of the family Filoviridae. No vaccine or established effective therapy currently is available for this catastrophic disease. AVI-6003 is an experimental combination of two phosphorodiamidate morpholino oligomers with positive charges (PMOplus™) that specifically target viral messenger RNA (mRNA) encoding MARV proteins. AVI-6003 has demonstrated evidence of protection against lethal infection in experimental mouse, guinea pig and non-human primate models of MARV infection. The objective of this clinical study is to determine the safety, tolerability and pharmacokinetics of intravenous administration of AVI-6003 in healthy human subjects over a dose range predicted to cover a therapeutic dose.

Methods: In this first-in-man study, up to 30 healthy male and female subjects between 18 and 50 years of age will be enrolled in 6 dose escalation cohorts of 5 subjects each and receive a single intravenous infusion of AVI-6003 or matched placebo in a 4:1 ratio. The expected dose escalation schedule is 0.01, 0.1, 1.0, 3.0, 6.0 and 9.0 mg/kg. Safety will be monitored through adverse event collection, telemetry, oximetry, serial blood and urine tests and electrocardiograms.

Results: Dosing of the first subjects has begun. Preliminary data from the initial dose cohorts will be presented.

Conclusion: This first-in-man phase 1 study will evaluate the safety, tolerability and pharmacokinetics of AVI-6003, a PMOplus™ compound that has demonstrated efficacy in animal models of MARV infection.

This work is supported by a contract with the Department of Defense Joint Project Manager Transformational Medical Technologies (JMP-TMT), W9113M-10-C-0056.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Tim Axtelle1, Apinya Vutikullird, DO2, Alison Heald, MD1 and Stephen Shrewsbury, MD1, (1)Clinical, AVI BioPharma, Bothell, WA, (2)West Coast Clinical Trials, Cypress, CA

Disclosures:

T. Axtelle, AVI BioPharma: Employee, Salary

A. Vutikullird, AVI BioPharma: Investigator, Salary

A. Heald, AVI BioPharma: Employee, Salary

S. Shrewsbury, AVI BioPharma: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.