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

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, 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.

Results:

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]).

Conclusion:

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