1955. A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of Caspofungin vs. Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants ≤3 Months of Age

Abstract

Background Candida species are the most common fungal pathogens in infants aged <1 year. Current antifungal regimens such as amphotericin B deoxycholate (dAmB) are associated with serious toxicity and multiple drug-drug interactions. The echinocandin caspofungin has less toxicity than dAmB and is approved for candidemia and other invasive Candida infections (ICI) in pediatric populations aged ≥3 months to 17 years. We investigated the efficacy of caspofungin in patients aged ≤3 months in ICI.MethodsThis phase 2, multicenter, randomized, double-blind, comparator-controlled study (Protocol MK0991-064; NCT01945281) enrolled patients aged ≤3 months with culture-confirmed ICI ≤96 hours before study entry. Patients were randomized 2:1 to IV caspofungin 2 mg/kg once daily or IV dAmB 1 mg/kg once daily. Primary endpoint was fungal-free survival (FFS) at 2 weeks post-therapy. Initial target sample size was 90 patients.ResultsFifty-one patients were enrolled. The study was terminated early due to low enrollment after >3.5 years’ recruitment. Median age (min–max) at enrollment = 22 days (7–88 days); male = 53.2%; median birth weight (min–max) = 1445 g (510–4,175 g); median baseline weight (min–max) = 1,860 g (425–6,540 g); median gestational age (min–max) = 30.4 weeks (26–41 weeks). C. albicans was the most common species isolated. Forty-nine patients received treatment (caspofungin, N = 33; dAmB, N = 16); two additional patients did not have confirmed infections at study entry. Overall, 47 patients were included in the full analysis set population (caspofungin, N = 31; dAmB, N = 16). FFS at 2 weeks post-therapy was 71.0% (22/31) in the caspofungin arm and 68.8% (11/16) in the dAmB arm (difference, –0.9% [95% CI, –24.3%, 27.7%]). 84.8% (28/33) of patients in the caspofungin arm and 100% (16/16) in the dAmB arm had ≥1 adverse event (AE); anemia (10/33 and 8/16, respectively) and sepsis (3/33 and 5/16, respectively) were the most common. Two patients in each arm had investigator-assessed treatment-related AEs. Serious AEs (SAEs) were 21.2% (7/33) in the caspofungin arm and 56.3% (9/16) in the dAmB arm; 5 patients died, 2 (6%) in caspofungin arm, and 3 (19%) in dAmB arm. All SAEs and deaths were unrelated to study drug.ConclusionAmong neonates and infants with confirmed ICI, FFS at 2 weeks was similar in the caspofungin and dAmB treatment arms. Patients who received caspofungin experienced fewer AEs and SAEs.Disclosures J. Kim, Merck & Co., Inc.: Employee, Salary. F. Lambey Nakwa, Merck & Co., Inc.: Principal Investigator, Research support. F. De Araujo Motta, Merck & Co., Inc.: Grant Investigator, Grant recipient. P. Salcedo Lozada, Merck & Co., Inc.: Investigator, Research support. D. Alabaz, Merck & Co., Inc.: Investigator, Research support. H. Liu, Merck & Co., Inc.: Employee, Salary. K. Bloise, Merck & Co., Inc.: Employee, Salary. M. B. Dorr, Merck & Co., Inc.: Employee and Shareholder, Salary. L. J. Anderson Gaffney, Merck & Co., Inc.: Employee, Salary. N. Kartsonis, Merck & Co., Inc.: Employee and Shareholder, Salary.