Program Schedule

1210
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 Neutropenic Patients

Session: Oral Abstract Session: Fungal Infections
Friday, October 10, 2014: 2:00 PM
Room: The Pennsylvania Convention Center: 109-AB
Background: Isavuconazole (ISA) is a novel, broad-spectrum, triazole antifungal available as a water-soluble prodrug 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). Neutropenia is linked to significant morbidity and mortality in patients with IMD. We present outcomes in patients with and without neutropenia at baseline from this trial.

Methods: Patients with proven/probable/possible IMD (EORTC/MSG criteria) were randomized 1:1 to receive ISA or VRC for up to 84 days. Dosing regimens were: ISA 200mg IV TID for 2 days, then 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 endpoint was all-cause mortality through Day 42. Overall success at end-of-treatment (EOT) as determined by an independent data-review committee (DRC), safety, and tolerability were also analyzed. Neutropenia was defined as per EORTC/MSG criteria.

Results: Patient characteristics, efficacy, and safety outcomes are shown in Table 1.

Conclusion: ISA has comparable efficacy to VRC for the primary treatment of IMD in neutropenic and non-neutropenic patients and may be better tolerated.

Table 1.Patient characteristics and outcomes

Neutropenic

Non-neutropenic

 

ISA

 

VRC

 

ISA

 

VRC

 

All treated patients (ITT), n

163

175

94

84

Proven/probable IMD (mITT), n

88

73

55

56

Efficacy

 

 

 

 

 

 

 

ISA

n (%)

VRC

n (%)

Adjusted difference*

% (95% CI)

ISA

n (%)

VRC

n (%)

Adjusted difference*

% (95% CI)

All-cause mortality Day 42

 

 

 

 

 

 

  ITT

34 (21)

37 (21)

–0.2

(–8.7, 8.3)

14 (15)

15 (18)

–4.0

(–14.2, 6.2)

  mITT

22 (25)

17 (23)

2.4

(–10.2, 14.9)

6 (11)

13 (23)

–13.5

(–26.8, –0.3)

Overall success EOT

 

 

 

 

 

 

  ITT

67 (41)

75 (43)

2.2

(–8.3, 12.8)

24 (25)

23 (28)

1.0

(–13.2, 15.2)

  mITT

34 (39)

29 (40)

0.4

(–14.0, 14.7)

16 (29)

18 (32)

2.5

(–13.3, 18.2)

Safety

 

 

 

 

AEs, n (%)

  ITT

  mITT

158 (97)

85 (97)

172 (98)

71 (97)

89 (95)

53 (96)

83 (99)

55 (98)

Drug-related AEs, n (%)

  ITT

  mITT

70 (43)

35 (40)

101 (58)

41 (56)

39 (42)

22 (40)

54 (64)

38 (68)

*ISA–VRC (VRC–ISA for overall success)

ITT, intent-to-treat population (patients who received ≥1 dose of study drug); mITT, modified intent-to-treat population (patients in ITT with proven/probable IMD as assessed by DRC)

Thomas Patterson1, Dominik Selleslag2, Kathleen Mullane3, Oliver Cornely4, William Hope5, Olivier Lortholary6, Bernhardt Zeiher7, Rochelle Maher7, Misun Lee7, Wenmei Huang7 and Dimitrios Kontoyiannis8, (1)The University of Texas Health Science Center, San Antonio, TX, (2)A.Z. Sint-Jan, Brugge, Belgium, (3)University of Chicago Medicine, Chicago, IL, (4)Uniklinik koln, Cologne, Germany, (5)Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom, (6)., Institut Pasteur, Paris, France, (7)Astellas Pharma Global Development, Northbrook, IL, (8)The University of Texas MD Anderson Cancer Center, Houston, TX

Disclosures:

T. Patterson, Astellas: Consultant and Scientific Advisor, Consulting fee

D. Selleslag, Pfizer: Investigator and Speaker's Bureau, Educational grant, Research grant and Speaker honorarium
Astellas: Investigator, Research support

K. Mullane, Astellas: Research Contractor and Speaker's Bureau, Research support
Pfizer: Research Contractor, Research support

O. Cornely, Astellas: Investigator and Scientific Advisor, Consulting fee, Research grant and Speaker honorarium
Pfizer: Investigator and Scientific Advisor, Consulting fee, Research grant and Speaker honorarium
Basilea: Consultant and Investigator, Consulting fee and Research grant

W. Hope, Astellas: Grant Investigator, Investigator and Scientific Advisor, Consulting fee, Grant recipient and Research grant
Pfizer: Grant Investigator, Consulting fee and Research support

O. Lortholary, Astellas: Investigator, Research support
Pfizer: Speaker's Bureau, Speaker honorarium

B. Zeiher, Astellas: Employee, Salary

R. Maher, Astellas Pharma Global Development: Employee, Salary

M. Lee, Astellas: Employee, Salary

W. Huang, Astellas: Employee, Salary

D. Kontoyiannis, Astellas: Investigator, Research grant and Research support
Pfizer: Investigator, Research grant and Speaker honorarium

See more of: Fungal Infections
See more of: Oral Abstract Session
Previous Abstract | Next Abstract >>

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

Sponsoring Societies:

© 2014, idweek.org. All Rights Reserved.

Follow IDWeek