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Randomized Controlled Trial
. 2022 Nov 15;66(11):e0095122.
doi: 10.1128/aac.00951-22. Epub 2022 Oct 31.

Safety and Pharmacokinetics of LHF-535, a Potential Treatment for Lassa Fever, in Healthy Adults

Sean M Amberg  1 , Benjamin Snyder  2   3 , Portia A Vliet-Gregg  1 , Eric J Tarcha  1 , Jeff Posakony  1 , Kristin M Bedard  1 , Alison E Heald  1   4
Affiliations
Randomized Controlled Trial

Safety and Pharmacokinetics of LHF-535, a Potential Treatment for Lassa Fever, in Healthy Adults

Sean M Amberg et al. Antimicrob Agents Chemother. .

Abstract

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.

Keywords: Lassa fever; antiviral agents; antiviral pharmacology.

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Conflict of interest statement

The authors declare a conflict of interest. All Kineta authors (S.M.A., P.A.V.-G., E.J.T., J.P., K.M.B., and A.E.H.) are or were employees or consultants to Kineta, Inc., and may have some equity in the company. Funding was received from the Wellcome Trust.

Figures

FIG 1
FIG 1
Mean plasma LHF-535 concentration in the phase 1a SAD study.
FIG 2
FIG 2
Mean plasma LHF-535 concentration in the phase 1b MAD study; overlay of days 1 and 14. * for 1125 mg group, participants received a loading dose of 2250 mg once on day 1, followed by a maintenance dose of 1125 mg/day on days 2 through 14.
FIG 3
FIG 3
Mean trough plasma LHF-535 concentration in the phase 1b MAD study. Each point represents the mean concentration 24 h after the last dose and immediately prior to the next dose. * for 1125 mg group, participants received a loading dose of 2250 mg once on day 1, followed by a maintenance dose of 1125 mg/day on days 2 through 14.
See this image and copyright information in PMC

References

    1. McCormick JB. 1987. Epidemiology and control of Lassa fever. Curr Top Microbiol Immunol 134:69–78. 10.1007/978-3-642-71726-0_3. - DOI - PubMed
    1. McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. 1987. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 155:437–444. 10.1093/infdis/155.3.437. - DOI - PubMed
    1. Grange ZL, Goldstein T, Johnson CK, Anthony S, Gilardi K, Daszak P, Olival KJ, O'Rourke T, Murray S, Olson SH, Togami E, Vidal G, Mazet JAK, Expert Panel, PREDICT Consortium . 2021. Ranking the risk of animal-to-human spillover for newly discovered viruses. Proc Natl Acad Sci USA 118:e2002324118. 10.1073/pnas.2002324118. - DOI - PMC - PubMed
    1. Akpede GO, Asogun DA, Okogbenin SA, Dawodu SO, Momoh MO, Dongo AE, Ike C, Tobin E, Akpede N, Ogbaini-Emovon E, Adewale AE, Ochei O, Onyeke F, Okonofua MO, Atafo RO, Odia I, Adomeh DI, Odigie G, Ogbeifun C, Muoebonam E, Ihekweazu C, Ramharter M, Colubri A, Sabeti PC, Happi CT, Günther S, Agbonlahor DE. 2019. Caseload and case fatality of Lassa fever in Nigeria, 2001–2018: a specialist center's experience and its implications. Front Public Health 7:170. 10.3389/fpubh.2019.00170. - DOI - PMC - PubMed
    1. Duvignaud A, Jaspard M, Etafo IC, Gabillard D, Serra B, Abejegah C, le Gal C, Abidoye AT, Doutchi M, Owhin S, Séri B, Vihundira JK, Bérerd-Camara M, Schaeffer J, Danet N, Augier A, Ogbaini-Emovon E, Salam AP, Ahmed LA, Duraffour S, Horby P, Günther S, Adedosu AN, Ayodeji OO, Anglaret X, Malvy D, LASCOPE Study Group . 2021. Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study. Lancet Glob Health 9:e469–e478. 10.1016/S2214-109X(20)30518-0. - DOI - PMC - PubMed

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