Antiviral activity of oral JNJ-53718678 in healthy adult volunteers challenged with respiratory syncytial virus: A placebo-controlled study

Marita Stevens, Sarah Rusch, John Devincenzo, Young In Kim, Lisa Harrison, Elizabeth A. Meals, Alison Boyers, Juin Fok-Seang, Dymphy Huntjens, Nacer Lounis, Kris Mariën, Bart Remmerie, Dirk Roymans, Anil Koul, Rene Verloes

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)748-756
Number of pages9
JournalJournal of Infectious Diseases
Volume218
Issue number5
DOIs
StatePublished - Jan 1 2018

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Respiratory Syncytial Viruses
Viral Load
Antiviral Agents
Healthy Volunteers
Placebos
Virus Shedding
Nose
Area Under Curve
Respiratory Syncytial Virus Infections
Urticaria
Virus Diseases
Electrocardiography
Therapeutics
RNA
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Antiviral activity of oral JNJ-53718678 in healthy adult volunteers challenged with respiratory syncytial virus : A placebo-controlled study. / Stevens, Marita; Rusch, Sarah; Devincenzo, John; Kim, Young In; Harrison, Lisa; Meals, Elizabeth A.; Boyers, Alison; Fok-Seang, Juin; Huntjens, Dymphy; Lounis, Nacer; Mariën, Kris; Remmerie, Bart; Roymans, Dirk; Koul, Anil; Verloes, Rene.

In: Journal of Infectious Diseases, Vol. 218, No. 5, 01.01.2018, p. 748-756.

Research output: Contribution to journalArticle

Stevens, M, Rusch, S, Devincenzo, J, Kim, YI, Harrison, L, Meals, EA, Boyers, A, Fok-Seang, J, Huntjens, D, Lounis, N, Mariën, K, Remmerie, B, Roymans, D, Koul, A & Verloes, R 2018, 'Antiviral activity of oral JNJ-53718678 in healthy adult volunteers challenged with respiratory syncytial virus: A placebo-controlled study', Journal of Infectious Diseases, vol. 218, no. 5, pp. 748-756. https://doi.org/10.1093/infdis/jiy227
Stevens, Marita ; Rusch, Sarah ; Devincenzo, John ; Kim, Young In ; Harrison, Lisa ; Meals, Elizabeth A. ; Boyers, Alison ; Fok-Seang, Juin ; Huntjens, Dymphy ; Lounis, Nacer ; Mariën, Kris ; Remmerie, Bart ; Roymans, Dirk ; Koul, Anil ; Verloes, Rene. / Antiviral activity of oral JNJ-53718678 in healthy adult volunteers challenged with respiratory syncytial virus : A placebo-controlled study. In: Journal of Infectious Diseases. 2018 ; Vol. 218, No. 5. pp. 748-756.
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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.",
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AU - Kim, Young In

AU - Harrison, Lisa

AU - Meals, Elizabeth A.

AU - Boyers, Alison

AU - Fok-Seang, Juin

AU - Huntjens, Dymphy

AU - Lounis, Nacer

AU - Mariën, Kris

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AU - Koul, Anil

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N2 - 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.

AB - 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.

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