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A Phase 3, Randomized, Double-Blind, Non-Inferiority Trial to Evaluate Efficacy and Safety of Isavuconazole versus Voriconazole in Patients with Invasive Mold Disease (SECURE): Outcomes in Invasive Aspergillosis Patients
Session: Oral Abstract Session: Fungal Infections
Methods: Patients were randomized 1:1 to receive ISA or VRC for up to 84 days. Dosing regimens were: ISA 200mg IV TID for 2 days, followed by 200mg QD (IV or PO); VRC 6mg/kg IV BID on Day 1, 4mg/kg IV BID on Day 2, then either 4mg/kg IV BID or 200mg PO BID. The primary efficacy endpoint was all-cause mortality (ACM) through Day 42. Overall success at end of treatment (EOT) and safety were also assessed. All diagnoses and outcomes were assessed by an independent, blinded, data-review committee. Safety data are presented as reported by the Investigator.
Results: Overall 231 patients were included in this analysis (ISA n=123; VRC n=108). Patient characteristics, efficacy, and safety outcomes are shown in Table 1. Differences in drug-related AEs between ISA and VRC were statistically significant (p<0.001).
Table 1.Patient characteristics and outcomes
|
ISA (n=123) |
VRC (n=108) |
Patient characteristics |
|
|
Age (years), mean ± SD |
51 ± 16 |
52 ± 15 |
Male, n (%) |
69 (56) |
71 (66) |
Primary underlying condition, n (%) |
|
|
Acute myeloid leukemia Acute lymphocytic leukemia Non-Hodgkin’s lymphoma Other |
44 (36) 15 (12) 14 (11) 49 (40) |
47 (44) 9 (8) 2 (2) 49 (45) |
Outcome – Efficacy |
|
|
ACM on Day 42, n (%) |
23 (19) |
24 (22) |
Adjusted difference (ISA–VRC), % (95% CI) |
−2.7 (−12.9, 7.5) |
|
ACM on Day 84 |
35 (29) |
39 (36) |
Adjusted difference (ISA–VRC), % (95% CI) |
−5.7 (−17.1, 5.6) |
|
Overall success at EOT, n (%) |
43 (35) |
42 (39) |
Adjusted difference (VRC–ISA), % (95% CI) |
4.0 (−8.0, 15.9) |
|
Outcome – Safety, n (%) |
|
|
AEs |
118 (96) |
106 (98) |
Drug-related AEs |
48 (39) |
67 (62) |
Serious AEs |
71 (58) |
71 (66) |
Drug-related serious AEs |
16 (13) |
13 (12) |
AEs leading to discontinuation |
22 (18) |
26 (24) |
Conclusion: In patients with documented IA, ISA had comparable efficacy to VRC, but was better tolerated than the latter.
Disclosures:
D. Kontoyiannis,
Merck, Inc.: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium
Astellas: Data review committee lead and Investigator, Compensaiton of data review committee involvement and Research grant
Pfizer: Investigator and Speaker's Bureau, Research grant and Speaker honorarium
M. Lee, Astellas: Employee, Salary
M. Nucci, Pfizer: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
Astellas: Scientific Advisor, Consulting fee
I. Raad, Astellas: Grant Investigator, Grant recipient
Pfizer: Consultant, Consulting fee
E. Bow, Astellas: Scientific Advisor, Consulting fee
Pfizer: Investigator and Scientific Advisor, Consulting fee and Research grant
V. A. Morrison, Astellas: Adjucation committee member, Consulting fee
J. Baddley, Astellas: Consultant, Consulting fee
Merck: Consultant, Consulting fee
Pfizer: Consultant, Consulting fee
B. Zeiher, Astellas: Employee, Salary
R. Maher, Astellas: Employee, Salary
W. Huang, Astellas: Employee, Salary
K. A. Marr, Astellas: Consultant and Scientific Advisor, Consulting fee
Merck: Consultant, Consulting fee
Pfizer: Consultant, Consulting fee