Safety and Efficacy of AK0529 in Respiratory Syncytial Virus-Infected
Infant Patients: a Phase 2 Proof-of-Concept Trial
Abstract
Background. Respiratory syncytial virus (RSV) infection is a cause of
substantial morbidity and mortality in young children. There is
currently no effective therapy available. Methods. This was a phase 2
study of the oral RSV fusion protein inhibitor AK0529 in infants aged
1-24 months, hospitalized with RSV infection. In part 1 patients (n=24)
were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or
placebo. In part 2 patients (n=48) were randomized 2:1 to receive AK0529
at 0.5, 1 or 2 mg/kg bid or placebo for five days. Sparse
pharmacokinetic samples were assessed using population pharmacokinetics
modelling. Safety, tolerability, viral load, signs and symptoms were
assessed daily during treatment. Results. No safety or tolerability
signals were detected for AK0529: grade ≥3 treatment-emergent adverse
events occurred in 4.1% of patients in AK0529 and 4.2% in placebo
groups, respectively, and none led to death or withdrawal from the
study. In part 2, targeted drug exposure was reached with 2 mg/kg bid. A
numerically greater reduction in median viral load with 2 mg/kg bid
AK0529 than with placebo at 96 hours was observed. A -4.0 (95% CI:
-4.51, -2.03) median reduction in RSV signs and symptom score from
baseline to 96 hours was observed in the 2 mg/kg group, compared with
-2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions. AK0529
was well tolerated in hospitalized RSV-infected infants. Treatment with
AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs
and symptoms.