Program Schedule

1211
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
Friday, October 10, 2014: 2:15 PM
Room: The Pennsylvania Convention Center: 109-AB
Background: Isavuconazole (ISA) is a novel, water-soluble, broad-spectrum triazole antifungal available in IV and oral formulations for treatment of invasive fungal disease. A Phase 3 trial (NCT00412893) assessed the efficacy and safety of ISA vs. voriconazole (VRC) in patients with invasive mold disease (IMD). Here we report on a pre-specified subset of patients from this trial who had proven/probable invasive aspergillosis (IA) (EORTC/MSG criteria) and received ≥1 dose of the study drug.

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.

Dimitrios Kontoyiannis1, Michael Giladi2, Misun Lee3, Marcio Nucci4, Issam Raad5, Eric Bow6, Vicki a. Morrison7, John Baddley8, Bernhardt Zeiher3, Rochelle Maher3, Wenmei Huang3 and Kieren a. Marr9, (1)Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, (2)Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, (3)Astellas Pharma Global Development, Northbrook, IL, (4)Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro - RJ, Brazil, (5)Infectious Diseases, Infection Control & Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX, (6)CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada, (7)University of Minnesota, VAMC, Minneapolis, MN, (8)Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (9)Departments of Medicine and Oncology, Johns Hopkins University, Baltimore, MD

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. Giladi, None

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

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