Article

 

IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSlideSet.pptx Public Deposited

Downloadable Content

Download file
https://ir.library.oregonstate.edu/concern/articles/5h73px82v

Descriptions

Attribute NameValues
Creator
Abstract
  • BACKGROUND: AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined. METHODS: We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized, multiple-ascending-dose study in which 40 healthy humans (8 humans per dose group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or 16 mg per kilogram of body weight) or placebo, in a 3: 1 ratio. We estimated the protective dose in humans by comparing pharmacokinetic variables in infected nonhuman primates, uninfected nonhuman primates, and uninfected humans. RESULTS: Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P < 0.001 with the use of the log-rank test for the comparison of survival across groups). No safety concern was identified at doses up to 16 mg per kilogram per day in humans. No serious adverse events were reported. Drug exposure (the area under the curve) was dose-dependent in both nonhuman primates and humans; drug clearance was independent of dose but was higher in nonhuman primates than in humans. The protective dose in humans was initially estimated, on the basis of exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to 12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram per day to match the geometric mean protective exposure in nonhuman primates. CONCLUSIONS: This study shows that, on the basis of efficacy in nonhuman primates and pharmacokinetic data in humans, AVI-7288 has potential as postexposure prophylaxis for MARV infection in humans.
Rights Statement
Additional Information
  • description.provenance : Made available in DSpace on 2015-08-12T16:21:33Z (GMT). No. of bitstreams: 5 IversenPatrickEnvirMoleToxAVI-7288MarburgVirus.pdf: 827976 bytes, checksum: beac86f613cf5663885d1b2fb41ee024 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSlideSet.pptx: 937633 bytes, checksum: ed0d4c915a3cf2ef5d39e51bc6b04f92 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryAppendix.pdf: 612777 bytes, checksum: 2525e5beaf74518bde927a2e6887e99a (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryDisclosures.pdf: 536331 bytes, checksum: cc6141faf8536fa5c52d2b9b1ee49c1b (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryProtocol.pdf: 3896696 bytes, checksum: 1089a352da08493b0405086f78fb3818 (MD5) Previous issue date: 2015-07-23
  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-08-12T16:21:11Z No. of bitstreams: 5 IversenPatrickEnvirMoleToxAVI-7288MarburgVirus.pdf: 827976 bytes, checksum: beac86f613cf5663885d1b2fb41ee024 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSlideSet.pptx: 937633 bytes, checksum: ed0d4c915a3cf2ef5d39e51bc6b04f92 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryAppendix.pdf: 612777 bytes, checksum: 2525e5beaf74518bde927a2e6887e99a (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryDisclosures.pdf: 536331 bytes, checksum: cc6141faf8536fa5c52d2b9b1ee49c1b (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryProtocol.pdf: 3896696 bytes, checksum: 1089a352da08493b0405086f78fb3818 (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-08-12T16:21:33Z (GMT) No. of bitstreams: 5 IversenPatrickEnvirMoleToxAVI-7288MarburgVirus.pdf: 827976 bytes, checksum: beac86f613cf5663885d1b2fb41ee024 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSlideSet.pptx: 937633 bytes, checksum: ed0d4c915a3cf2ef5d39e51bc6b04f92 (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryAppendix.pdf: 612777 bytes, checksum: 2525e5beaf74518bde927a2e6887e99a (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryDisclosures.pdf: 536331 bytes, checksum: cc6141faf8536fa5c52d2b9b1ee49c1b (MD5) IversenPatrickEnvirMoleToxAVI-7288MarburgVirusSupplementaryProtocol.pdf: 3896696 bytes, checksum: 1089a352da08493b0405086f78fb3818 (MD5)

Relationships

Parents:

Items