Phase 2, open-label, noncomparative clinical trial evaluating safety and efficacy of posaconazole in pediatric patients with proven/probable invasive aspergillosis or possible invasive fungal disease

Children with invasive aspergillosis (IA) experience significant morbidity and mortality. Posaconazole is a broad-spectrum triazole antifungal agent indicated for IA treatment in adolescents and adults. A phase 2, open-label, noncomparative, multinational clinical trial in pediatric participants (2-to-<18 years old, body weight ≥10 kg) with possible, probable, or proven IA was conducted. Participants received intravenous posaconazole for ≥1 week, after which they could switch to oral posaconazole for a total treatment duration <u><</u>12 weeks. Posaconazole dosing and selection of oral formulation (tablet or oral suspension [PFS]) were weight-based. The primary endpoint was safety, assessed as treatment-related adverse events (TRAE) through 14 days after treatment cessation. Global clinical response was a secondary and all-cause mortality an exploratory endpoint. PFS palatability was assessed using a 5-point scale. Thirty-one participants (proven/probable IA <i>n</i> = 9, possible invasive fungal disease <i>n</i> = 22) received ≥1 dose of posaconazole; 14 were 2 to <12 years, and 17 were 12 to <18 years old. Median treatment duration was 49 (range: 2-88) days. Seven participants (22.6%; 95% confidence interval [CI]: 9.6, 41.1) had ≥1 TRAE (grade 1 or 2, all resolved). One participant discontinued treatment due to a nonserious TRAE. Favorable global clinical response rates through weeks 6 and 12 were 67.7% (95% CI: 48.6, 83.3) and 77.4% (95% CI: 58.9, 90.4), respectively (no relapses). Day 114 all-cause mortality was 12.9%. No participants experienced problems taking PFS, and 90.0% rated PFS palatability as very good to neutral. Posaconazole was well tolerated and associated with high clinical response rates in pediatric patients with IA.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04218851.