1354. Safety and tolerability of 514G3, a True Human Anti-Protein A Monoclonal Antibody for the treatment of S. aureus Bacteremia.
Session: Poster Abstract Session: Clinical Trials
Friday, October 28, 2016
Room: Poster Hall
Posters
  • 1354_IDWPOSTER.pdf (8.1 MB)
  • Background:

    Novel therapeutic approaches are urgently needed for the treatment of serious infections due to S. aureus. 514G3 is a True Human Monoclonal antibody (IgG3), targeting Staphylococcus Protein A (SpA), which was isolated and cloned from a healthy human donor. Treatment of S. aureus infection with a True Human Antibody is expected to be safe, with minimal side effects.

    Methods:

    Phase I, double blind, multicenter, randomized, placebo controlled, dose escalation study of 514G3 in patients hospitalized with S. aureus bacteremia. Eligible subjects received a single intravenous dose of 514G3 at 2, 10, or 40 mg/kg or placebo (3:1) along with standard antibiotic therapy. Subjects were followed for at least 14 days to assess adverse events (AEs), potential dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD). DLTs were defined as any grade 3 or greater AE assessed as probably or definitely related to therapy. The MTD was defined as the highest dose level with ≤1 DLT.

    Results:

    12 subjects received 514G3, and 4 placebo. Median age was 60, and 39% were female. Infection source was skin and soft tissue infection (6), phlebitis or catheter associated (4), unknown (3), and hemodialysis vascular access (3). MRSA was identified in 6 of 16 patients (38%). No DLTs occurred. The MTD was undefined, and 40 mg/kg was designated as the recommended phase 2 dose. The incidence of SAEs was lower in the 514G3 group than placebo, with 3 of 12 (25%) and 2 of 4 (50%) experiencing SAEs respectively. None of the SAEs were probably or definitely related to antibody therapy, and all were deemed to be related to worsening of the patients’ underlying condition.

    Conclusion:

    514G3 was safe and well tolerated at all dose levels tested. While the numbers are small, fewer SAEs in the 514G3 treatment group suggest a favorable side effect and tolerability profile. Safety and reduction of complications from S. aureus bacteremia will be explored further in a randomized controlled trial utilizing the 40 mg/kg dose that is adequately powered to demonstrate differences between treatment arms.

    Toan Huynh, MD, Carolinas Healthcare System/F.H. Sammy Ross Trauma Center, Charlotte, NC, Michael Stecher, MD, Clinical Regulatory, XBiotech USA, Inc, Austin, TX, John Mckinnon, MD, MSc, Medicine / Infectious Diseases, Henry Ford Hospital, Detroit, MI, Norma Jung, MD, University of Koln, Koln, Germany and Mark E. Rupp, MD, FIDSA, FSHEA, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE

    Disclosures:

    T. Huynh, None

    M. Stecher, XBiotech: Employee and Shareholder , Salary

    J. Mckinnon, None

    N. Jung, Labor Stein: Speaker's Bureau , Speaker honorarium
    Novartis: Speaker's Bureau , Speaker honorarium and travel grant
    Astellas: Consultant , travel grant
    Infectofos: Grant Investigator , Research grant

    M. E. Rupp, None

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