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J Infect Dis. 2018 Jul 24;218(5):748-756. doi: 10.1093/infdis/jiy227.

Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study.

Author information

1
Janssen Research & Development, Beerse, Belgium.
2
Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis.
3
Department of Pediatrics, University of Tennessee School of Medicine, Memphis.
4
Department of Microbiology, Immunology, and Biochemistry, University of Tennessee School of Medicine, Memphis.
5
hVIVO Services Limited, Queen Mary Bioenterprises Innovation Centre, London, United Kingdom.

Abstract

Background:

Respiratory syncytial virus (RSV) disease has no effective treatment. JNJ-53718678 is a fusion inhibitor with selective activity against RSV.

Methods:

After confirmation of RSV infection or 5 days after inoculation with RSV, participants (n = 69) were randomized to JNJ-53718678 75 mg (n = 15), 200 mg (n = 17), 500 mg (n = 18), or placebo (n = 17) orally once daily for 7 days. Antiviral effects were evaluated by assessing RSV RNA viral load (VL) area under the curve (AUC) from baseline (before the first dose) until discharge, time-to-peak VL, duration of viral shedding, clinical symptoms, and quantity of nasal secretions.

Results:

Mean VL AUC was lower for individuals treated with different doses of JNJ-53718678 versus placebo (203.8-253.8 vs 432.8 log10 PFUe.hour/mL). Also, mean peak VL, time to peak VL, duration of viral shedding, mean overall symptom score, and nasal secretion weight were lower in each JNJ-53718678-treated group versus placebo. No clear exposure-response relationship was observed. Three participants discontinued due to treatment-emergent adverse events of grade 2 and 1 electrocardiogram change (JNJ-53718678 75 mg and 200 mg, respectively) and grade 2 urticaria (placebo).

Conclusions:

JNJ-53718678 at all 3 doses substantially reduced VL and clinical disease severity, thus establishing clinical proof of concept and the compound's potential as a novel RSV treatment.

Clinical trials registration:

ClinicalTrials.gov: NCT02387606; EudraCT number: 2014-005041-41.

PMID:
29684148
DOI:
10.1093/infdis/jiy227
[Indexed for MEDLINE]

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