650. Effect of Oral JNJ-53718678 (JNJ-678) on Disease Severity in Healthy Adult Volunteers Experimentally Inoculated with Live Respiratory Syncytial Virus (RSV): A Placebo-Controlled Challenge Study
Session: Poster Abstract Session: Oh, Those Pesky Viruses!
Thursday, October 27, 2016
Room: Poster Hall


RSV infection causes substantial morbidity and mortality but has no effective therapy or vaccine. JNJ-678 is a fusion protein inhibitor, with selective and potent activity against RSV in vitro and in animal models. This study assessed antiviral effects and safety of orally administered JNJ-678, as well as its effect on RSV clinical symptoms, compared to placebo in a human challenge study.


Healthy volunteers (N=69) were inoculated with RSV-A Memphis 37b on Day 0. After a mean of 12.2 hours of qualitative RSV RNA positivity in nasal wash specimens, volunteers began randomized treatment. In the intent-to-treat-infected (ITT-I) population (quantifiable RSV viral load [VL] immediately prior to or twice after first treatment dose; N=45), 9 participants received 75mg JNJ-678 and 12 each received 200, 500mg JNJ-678 or placebo; QD for 7 days. Antiviral effects (RSV RNA VL AUC from baseline [last value prior to first dose] until discharge), effect on RSV clinical symptoms (symptom score self-assessment), nasal secretion weight, safety and tolerability were evaluated.


AUC VL (p=0.0167, 200mg) and peak VL were lower for JNJ‑678 recipients compared to placebo. After starting treatment, symptom scores over time in all JNJ-678 groups were lower than placebo (Figure 1). Mean (95% CI) overall total symptom scores were 6.4 (-12.3;25.2), 23.1 (6.9;39.3), 14.8
(-1.4;31.1) and 36.6 (20.4;52.8) for the 75, 200 and 500 mg JNJ-678 groups and placebo, respectively.

Duration of symptoms (time from baseline to first 24-hour period with symptom scores of 0) was shorter in the 75 and 200mg JNJ-678 groups compared to placebo (Figure 2). Mean total nasal secretions during treatment were lower in JNJ-678 recipients (1–3g) compared to placebo (5g).

Multiple doses of up to 500mg JNJ-678 QD were generally safe and well tolerated. No serious adverse events (AEs) were recorded during the study and no treatment-emergent Grade 3/4 AEs were observed during the treatment phase. Two participants discontinued due to an AE considered at least possibly related to RSV challenge or study drug by the investigator (urticaria [placebo] and nonspecific ECG change [200mg JNJ-678]).


JNJ-678 has potential as a novel RSV treatment, reducing VL and disease severity and duration.


Samuel Israel, PhD1, Sarah Rusch, MSc2, John DeVincenzo, MD3,4, Alison Boyers, MSc1, Juin Fok-Seang, BSc1, Dymphy Huntjens, PhD2, Nacer Lounis, PhD2, Kris Mariёn, MSc2, Marita Stevens, MD2 and René Verloes, MD2, (1)hVIVO Services Limited, Queen Mary Bioenterprises Innovation Centre, London, United Kingdom, (2)Janssen Research & Development, Beerse, Belgium, (3)Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, (4)Department of Pediatrics and Department of Microbiology, Immunology, and Biochemistry, University of Tennessee School of Medicine, Memphis, TN


S. Israel, None

S. Rusch, Janssen: Employee , Salary

J. DeVincenzo, AstraZeneca: Research Contractor , Research grant
Regeneron Pharmaceuticals: Research Contractor , Research grant
Alios BioPharma: Research Contractor and Scientific Advisor , Consulting fee and Research grant
Biota: Research Contractor and Scientific Advisor , Consulting fee and Research grant
Gilead Sciences: Research Contractor and Scientific Advisor , Consulting fee and Research grant
Janssen: Research Contractor and Scientific Advisor , Consulting fee and Research grant
Teva Pharmaceuticals: Research Contractor and Scientific Advisor , Consulting fee and Research grant
Merck: Scientific Advisor , Consulting fee
Pulmocide: Research Contractor , Consulting fee and Research grant
Ark Pharmaceuticals: Scientific Advisor , Consulting fee

A. Boyers, Janssen: Employee , Salary

J. Fok-Seang, None

D. Huntjens, Janssen: Employee , Salary

N. Lounis, Janssen: Employee , Salary

K. Mariёn, Janssen: Employee and Shareholder , Salary and shares

M. Stevens, Janssen: Employee and Shareholder , Salary and stock and stock options

R. Verloes, Janssen: Employee , Salary

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.