Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JNJ-64794964, a TLR-7 agonist, in healthy adults

This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist, JNJ-64794964 (JNJ-4964) in healthy adults. In the SAD phase, participants received JNJ-4964 0.2 ( = 6), 0.6 ( = 6), 1.25 ( = 8) or 1.8 mg ( = 6) or placebo ( = 2/dose cohort) in a fasted state. Food effect was evaluated for the 1.25 mg cohort following ≥6 weeks washout. In the MD phase, participants received JNJ-4964 1.25 mg ( = 6) or placebo ( = 2) weekly (fasted) for 4 weeks. Participants were followed-up for 4 weeks. No serious adverse events (AEs) occurred. 10/34 (SAD) and 5/8 (MD) participants reported mild-to-moderate (≤Grade 2), transient, reversible AEs possibly related to JNJ-4964. Five (SAD) participants had fever/flu-like AEs, coinciding with interferon-α serum levels ≥100 pg/mL and lymphopenia (