| Autor: |
Amberg SM; Kineta, Inc., Seattle, Washington, USA., Snyder B; Nucleus Network Pty Ltd., Melbourne, Victoria, Australia.; Alfred Health, Melbourne, Victoria, Australia., Vliet-Gregg PA; Kineta, Inc., Seattle, Washington, USA., Tarcha EJ; Kineta, Inc., Seattle, Washington, USA., Posakony J; Kineta, Inc., Seattle, Washington, USA., Bedard KM; Kineta, Inc., Seattle, Washington, USA., Heald AE; Kineta, Inc., Seattle, Washington, USA.; University of Washington, Seattle, Washington, USA. |
| Abstrakt: |
LHF-535 is a small-molecule antiviral currently under development as a therapeutic option to treat Lassa fever and other viral hemorrhagic fevers of arenavirus origin. The human safety and pharmacokinetics of LHF-535 were evaluated in two phase 1 trials in healthy volunteers. The first study was a double-blind, single ascending dose trial that evaluated weight-based oral doses ranging from 0.3 mg/kg in the first cohort to 40 mg/kg in the last cohort. The second study was a double-blind, multiple ascending dose trial that evaluated a 14-day oral dosing regimen, with three sequential cohorts receiving fixed doses of 450, 900, or 1,125 mg per day; the third cohort (1,125 mg/day) received a higher (loading) dose of 2,250 mg for the first dose. Each cohort in both studies consisted of eight participants randomized to either placebo ( n = 2) or LHF-535 ( n = 6). LHF-535 was well tolerated in both studies. Treatment-emergent adverse events were more frequent in placebo recipients than in LHF-535 recipients in both studies. LHF-535 exhibited rapid absorption, a long half-life, and exposures predicted to suppress viral replication. |
