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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

Year: 2016

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Background. 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. Methods. 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, 500 mg 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. Results. AUC VL (p = 0.0167, 200 mg) 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 to 25.2), 23.1 (6.9 to 39.3), 14.8 (−1.4 to 31.1) and 36.6 (20.4 to 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 200 mg JNJ-678 groups compared to placebo (Figure 2). Mean total nasal secretions during treatment were lower in JNJ-678 recipients (1–3 grams) compared to placebo (5 grams). Multiple doses of up to 500 mg 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 [200 mg JNJ-678]). Conclusion. JNJ-678 has potential as a novel RSV treatment, reducing VL and disease severity and duration. Disclosures. 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; 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

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofw172.513