tetano
Editor, Senior Moderator
Antivir Ther. 2017 Dec 15. doi: 10.3851/IMP3212. [Epub ahead of print]
[h=1]JNJ-63623872 treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo-controlled study.[/h] Trevejo JM[SUP]1[/SUP], Asmal M[SUP]2[/SUP], Vingerhoets J[SUP]3[/SUP], Polo R[SUP]4[/SUP], Robertson S[SUP]5[/SUP], Jiang Y[SUP]6[/SUP], Kieffer TL[SUP]5[/SUP], Leopold L[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] JNJ-63623872 is a novel, non-nucleoside polymerase complex inhibitor with in vitro activity against influenza A virus, including pandemic 2009 H1N1, H7N9, H5N1 strains as well as neuraminidase-and amantadine-resistant strains.
[h=4]METHODS:[/h] Randomized, double-blind, placebo-controlled, Phase 2a study. Healthy volunteers (N = 104) were inoculated with an influenza A/Wisconsin/67/2005 (H3N2) challenge virus. 72 received JNJ-63623872 and 32 placebo. JNJ-63623872 was dosed for 5 days once daily from 24 hours after viral inoculation at four dose levels: 100 mg, 400 mg, loading dose 900/600 mg and loading dose 1200/600 mg.
[h=4]RESULTS:[/h] JNJ-63623872 significantly reduced viral shedding (AUC measured by TCID[SUB]50[/SUB] or qRT-PCR) versus placebo as measured by cell culture assay in the pooled analysis (Jonckheere-Terpstra dose-response trend test [P = 0.036]). Reductions were observed in viral shedding (AUC, duration and peak measured by grade), influenza-like symptoms (AUC, duration and peak measured by grade) and clinical symptoms (duration and peak measured by grade) for all JNJ-63623872 groups versus placebo, significantly so for the 1200/600 mg group. In the 1200/600 mg group viral shedding (AUC) by qRT-PCR was 0.45 versus 18.4 log[SUB]10[/SUB] copies/mL*Day for pooled placebo (P = 0.014). JNJ-63623872 was generally safe and well-tolerated with no SAEs or AEs leading to discontinuation.
[h=4]CONCLUSIONS:[/h] JNJ-63623872 has potential to not only reduce viral load but to have a clinical impact on patients as a novel treatment for influenza A virus infection. Further trials are therefore warranted to assess JNJ-63623872.
PMID: 29244026 DOI: 10.3851/IMP3212
[h=1]JNJ-63623872 treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo-controlled study.[/h] Trevejo JM[SUP]1[/SUP], Asmal M[SUP]2[/SUP], Vingerhoets J[SUP]3[/SUP], Polo R[SUP]4[/SUP], Robertson S[SUP]5[/SUP], Jiang Y[SUP]6[/SUP], Kieffer TL[SUP]5[/SUP], Leopold L[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] JNJ-63623872 is a novel, non-nucleoside polymerase complex inhibitor with in vitro activity against influenza A virus, including pandemic 2009 H1N1, H7N9, H5N1 strains as well as neuraminidase-and amantadine-resistant strains.
[h=4]METHODS:[/h] Randomized, double-blind, placebo-controlled, Phase 2a study. Healthy volunteers (N = 104) were inoculated with an influenza A/Wisconsin/67/2005 (H3N2) challenge virus. 72 received JNJ-63623872 and 32 placebo. JNJ-63623872 was dosed for 5 days once daily from 24 hours after viral inoculation at four dose levels: 100 mg, 400 mg, loading dose 900/600 mg and loading dose 1200/600 mg.
[h=4]RESULTS:[/h] JNJ-63623872 significantly reduced viral shedding (AUC measured by TCID[SUB]50[/SUB] or qRT-PCR) versus placebo as measured by cell culture assay in the pooled analysis (Jonckheere-Terpstra dose-response trend test [P = 0.036]). Reductions were observed in viral shedding (AUC, duration and peak measured by grade), influenza-like symptoms (AUC, duration and peak measured by grade) and clinical symptoms (duration and peak measured by grade) for all JNJ-63623872 groups versus placebo, significantly so for the 1200/600 mg group. In the 1200/600 mg group viral shedding (AUC) by qRT-PCR was 0.45 versus 18.4 log[SUB]10[/SUB] copies/mL*Day for pooled placebo (P = 0.014). JNJ-63623872 was generally safe and well-tolerated with no SAEs or AEs leading to discontinuation.
[h=4]CONCLUSIONS:[/h] JNJ-63623872 has potential to not only reduce viral load but to have a clinical impact on patients as a novel treatment for influenza A virus infection. Further trials are therefore warranted to assess JNJ-63623872.
PMID: 29244026 DOI: 10.3851/IMP3212