tetano
Editor, Senior Moderator
J Infect Dis. 2018 Jul 26. doi: 10.1093/infdis/jiy410. [Epub ahead of print]
[h=1]Antiviral Activity, Safety, and Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human Challenge Study.[/h] Yogaratnam J[SUP]1[/SUP], Rito J[SUP]1[/SUP], Kakuda TN[SUP]1[/SUP], Fennema H[SUP]2[/SUP], Gupta K[SUP]1[/SUP], Jekle CA[SUP]1[/SUP], Mitchell T[SUP]3[/SUP], Boyce M[SUP]3[/SUP], Sahgal O[SUP]3[/SUP], Balaratnam G[SUP]4[/SUP], Chanda S[SUP]1[/SUP], Van Remoortere P[SUP]5[/SUP], Symons JA[SUP]1[/SUP], Fry J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] AL-794 is an orally active prodrug of ALS-033719, which selectively inhibits the endonuclease domain of influenza virus A and B polymerase.
[h=4]Methods:[/h] In a phase 1, double-blinded, randomized, placebo-controlled study, healthy subjects were inoculated intranasally with influenza virus (A/Perth/16/2009 H3N2) after confirmation of infection or on day 4. Subjects received 50 mg of AL-794, 150 mg of AL-794, or placebo twice daily for 5 days. Viral load, influenza symptoms, pharmacokinetics, and safety were evaluated.
[h=4]Results:[/h] A total of 61 subjects were inoculated. In 42 infected subjects, the mean peak viral load for 50-mg AL-794 recipients, 150-mg AL-794 recipients, and placebo recipients was 3.54, 2.77, and 3.72 log10 50% tissue culture infectious doses (TCID50)/mL, respectively. The mean influenza viral load area under the curve in the corresponding treatment groups was 137, 87.5, and 142 log10 TCID50/mL?h, respectively, and the median time to virus nondetection was 117, 75.3, and 108 hours, respectively. AL-794 was well tolerated, and no viral resistance to ALS-033719 was identified.
[h=4]Conclusion:[/h] Following oral administration of AL-794, significant dose-dependent antiviral activity was noted, with a greater decrease in viral load, symptoms, and mucus weight at the 150-mg dose, compared with the 50-mg dose, and no safety concerns for either dose or placebo.
[h=4]Clinical Trials Registration:[/h] NCT02588521.
PMID: 30053042 DOI: 10.1093/infdis/jiy410
[h=1]Antiviral Activity, Safety, and Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human Challenge Study.[/h] Yogaratnam J[SUP]1[/SUP], Rito J[SUP]1[/SUP], Kakuda TN[SUP]1[/SUP], Fennema H[SUP]2[/SUP], Gupta K[SUP]1[/SUP], Jekle CA[SUP]1[/SUP], Mitchell T[SUP]3[/SUP], Boyce M[SUP]3[/SUP], Sahgal O[SUP]3[/SUP], Balaratnam G[SUP]4[/SUP], Chanda S[SUP]1[/SUP], Van Remoortere P[SUP]5[/SUP], Symons JA[SUP]1[/SUP], Fry J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] AL-794 is an orally active prodrug of ALS-033719, which selectively inhibits the endonuclease domain of influenza virus A and B polymerase.
[h=4]Methods:[/h] In a phase 1, double-blinded, randomized, placebo-controlled study, healthy subjects were inoculated intranasally with influenza virus (A/Perth/16/2009 H3N2) after confirmation of infection or on day 4. Subjects received 50 mg of AL-794, 150 mg of AL-794, or placebo twice daily for 5 days. Viral load, influenza symptoms, pharmacokinetics, and safety were evaluated.
[h=4]Results:[/h] A total of 61 subjects were inoculated. In 42 infected subjects, the mean peak viral load for 50-mg AL-794 recipients, 150-mg AL-794 recipients, and placebo recipients was 3.54, 2.77, and 3.72 log10 50% tissue culture infectious doses (TCID50)/mL, respectively. The mean influenza viral load area under the curve in the corresponding treatment groups was 137, 87.5, and 142 log10 TCID50/mL?h, respectively, and the median time to virus nondetection was 117, 75.3, and 108 hours, respectively. AL-794 was well tolerated, and no viral resistance to ALS-033719 was identified.
[h=4]Conclusion:[/h] Following oral administration of AL-794, significant dose-dependent antiviral activity was noted, with a greater decrease in viral load, symptoms, and mucus weight at the 150-mg dose, compared with the 50-mg dose, and no safety concerns for either dose or placebo.
[h=4]Clinical Trials Registration:[/h] NCT02588521.
PMID: 30053042 DOI: 10.1093/infdis/jiy410