Trial Information

Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia

The objective of this study is to evaluate the safety, tolerance, and pharmacokinetics of
FK463, a novel echinocandin (cell wall-active antifungal lipopeptide), as early empirical
therapy for prevention of fungal infections in immunocompromised children. The study is
designed as a multicenter open label, sequential dose escalation study of intravenous FK463.
Intravenous FK463 will be administered daily as a one hour infusion to patients with new
onset of fever and neutropenia (absolute neutrophil count less than or equal to 500/mm3) who
will be initiated onto broad spectrum empirical antibacterial therapy. The patient
population consists of children ages 2 to 17 years of age; two age cohorts will be studied
(2-12, 13-17). Dosage levels will be 0.5 mg/kg/day (not to exceed 25 mg/day), 1.0 mg/kg/day
(not to exceed 50 mg/day), 1.5 mg/kg/day (not to exceed 75 mg/day). 2.0 mg/kg/day (not to
exceed 100 mg/day), 3.0 mg/kg/day (not to exceed 150 mg/day) and 4.0 mg/kg/day (not to
exceed 200 mg/day). The planned sample size is 96 patients (a maximum of two replacement
patients may be added to a given dose level and age cohort, for a total of no more than 10
patients per dose level and age cohort. The study will enroll no more than 120 patients).
At each dosage level, a total of 8 patients will be enrolled into each age cohort (2-12,
13-17); a total of 16 patients will be enrolled at each dosage level. The first group of
patients will receive FK463 at 0.5 mg/kg/day (not to exceed 25 mg/day). The second group of
patients will receive 1.0 mg/kg/day (not to exceed 50 mg/day). The third group of patients
will receive 1.5 mg/kg/day (not to exceed 75 mg/day). The fourth group of patients will
receive 2.0 mg/kg/day (not to exceed 100 mg/day). The fifth group of patients will receive
3.0 mg/kg/day (not to exceed 150 mg/day). The sixth group of patients will receive 4.0
mg/kg/day (not to exceed 200 mg/day). Study drug will continue until recovery from
neutropenia (ANC post nadir greater than or equal 250/mm3) or until the initiation of
conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B for
empirical antifungal therapy or for proven fungal infection. Patients may receive FK463 for
a maximum duration of 14 days. For any patient who meets institutional criteria to start
standard empirical antifungal therapy with conventional deoxycholate amphotericin B or a
lipid formulation of amphotericin B (greater than 96 hours on study drug) or who has a
proven breakthrough fungal infection, FK463 will be discontinued and conventional
deoxycholate amphotericin B or a lipid formulation of amphotericin B will be initiated.