Program Schedule

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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 (IMD): Outcomes in Patients with Pulmonary Infections

Session: Poster Abstract Session: Clinical - Clinical Trials
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • Outcomes by Pulmonary Infections_FINAL.pdf (195.6 kB)
  • 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 assessed the efficacy and safety of ISA vs. voriconazole (VRC) in patients with IMD. Here we report outcomes in a pre-specified subset of patients from this non-inferiority trial, who had proven, probable, or possible pulmonary mold disease (PMD) without other site involvement (lower respiratory tract disease only).

    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. Eligibility criteria and pre-specified outcomes are available at clinicaltrials.gov, NCT00412893. The primary efficacy endpoint was all-cause mortality by Day 42. All-cause mortality on Day 84, overall success (complete + partial response) at end of treatment (EOT) determined by an independent blinded data review committee were recorded. Safety and tolerability were also assessed, as reported by the Investigator.

    Results: Overall 412 patients with proven/probable/possible PMD, primarily caused by Aspergillus spp. (n=224), were enrolled. Patient characteristics, outcomes, and adverse events (AEs) are presented in Table 1. Outcomes in patients with proven/probable cases were similar to those with proven/probable/possible infections.

    Table 1.Efficacy and safety in patients with PMD

    Parameter

    ISA (n=200)

    VRC (n=212)

    Adjusted difference* % (95% CI)

    All-cause mortality on Day 42

    34 (17)

    44 (21)

    −2.9 (−10.4, 4.6)

    All-cause mortality on Day 84

    55 (28)

    68 (32)

    −3.8 (−12.4, 4.8)

    Overall success at EOT

    82 (41)

    89 (42)

    −1.8 (−11.1, 7.4)

      Complete response

    28 (14)

    35 (17)

     

      Partial response

    54 (27)

    54 (25)

     

    Stable

    53 (27)

    60 (28)

     

    Progression

    65 (33)

    63 (30)

     

    Safety

     

     

    P value

      AEs

    194 (97)

    210 (99)

    0.2

      Study drug-related AEs

    85 (43)

    130 (61)

    <0.001

      Serious AEs

    108 (54)

    128 (60)

    0.2

      Study drug-related serious AEs

    24 (12)

    27 (13)

    0.9

      AE leading to permanent  discontinuation

    33 (17)

    53 (25)

    0.04

    *(ISA–VRC)

    Conclusion: ISA had comparable efficacy to VRC for the primary treatment of PMD patients, but had a lower rate of drug-related AEs vs. VRC

    Issam Raad1, Kathleen M. Mullane2, Dominik Selleslag3, George Thompson4, Dionissios Neofytos, MD5,6, Shmuel Shoham, MD5, Misun Lee7, Rochelle Maher7, Bernhardt Zeiher7 and Francisco M. Marty8, (1)University of Texas MD Anderson Cancer Center, Houston, TX, (2)The University of Chicago Medicine, Chicago, IL, (3)A.Z. Sint-Jan, Brugge, Belgium, (4)University of California, Davis, CA, (5)The Johns Hopkins Hospital, Baltimore, MD, (6)Memorial Sloan-Kettering Cancer Center, New York, NY, (7)Astellas Pharma Global Development, Northbrook, IL, (8)Brigham and Women's Hospital, Boston, MA

    Disclosures:

    I. Raad, Atellas: Grant Investigator, Grant recipient
    Pfizer: Consultant, Consulting fee

    K. M. Mullane, Astellas Pharma US, Inc.: Research Contractor and Speaker's Bureau, Research support
    Anson Pharmaceuticals: Research Contractor, Research support
    Chimerix: Research Contractor and Scientific Advisor, Research support
    Cubist / Optimer: Research Contractor, Scientific Advisor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
    Merck Sharp & Dohme Corp: Research Contractor and Scientific Advisor, Consulting fee and Research support
    Rebiotix: Research Contractor, Research support
    ViroPharma: Research Contractor, Research support
    Pfizer: Research Contractor, Research support

    D. Selleslag, Pfizer: Investigator and Speaker's Bureau, Educational grant, Research grant and Speaker honorarium
    MSD: Investigator and Scientific Advisor, Consulting fee and Research support
    Astellas: Investigator, Research support

    G. Thompson, Astellas: Scientific Advisor, Consulting fee

    D. Neofytos, Astellas: Consultant and Scientific Advisor, Consulting fee and Speaker honorarium
    Roche Diganostics: Scientific Advisor, Consulting fee
    Pfizer: Research Contractor, Research grant

    S. Shoham, Astellas: Scientific Advisor, Research support
    Merck: Grant Investigator, Grant recipient and Research support
    Pfizer: Investigator, Research support

    M. Lee, Astellas: Employee, Salary

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

    B. Zeiher, Astellas: Employee, Salary

    F. M. Marty, Astellas: Grant Investigator, Research support
    Chimerix: Grant Investigator, Research support
    Merck: Consultant, Consulting fee
    Vertex: Consultant, Consulting fee
    Whiscon: Grant Investigator, Research support
    Alexion: Consultant, Consulting fee
    Gilead: Consultant, Consulting fee
    ViroPharma: Grant Investigator, Research support
    GlaxoSmithKline: Grant Investigator, Research support

    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.

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