898. GEN-003 Phase 2 Interim Results:  Therapeutic Vaccine for Genital Herpes Significantly Reduces Viral Shedding and Genital Lesions
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall
Posters
  • ID Week Poster 898.VW.pdf (209.3 kB)
  • Background:  Genital HSV-2 infection is the most common cause of genital ulcers worldwide.  While not all infected persons report genital lesions, viral reactivation also occurs in the absence of lesions, and drives ongoing transmission.  

    GEN-003 is a candidate therapeutic vaccine containing recombinant HSV antigens gD and ICP4 along with Matrix M-2 (MM) adjuvant.   In a phase 1 / 2 study, GEN-003 demonstrated significant reductions in both genital lesions and viral shedding.  This Phase 2 study was designed to confirm the antiviral activity of GEN-003 in HSV-2 infected patients and select the best dose combination of antigen and adjuvant for future clinical trials.

    Methods:  We randomized healthy adults with symptomatic genital herpes in a matrix design to 30 or 60 µg of each protein antigen and 25, 50, or 75 µg MM, or saline placebo.  All participants received 3 vaccinations 3 weeks apart.  Participants collected twice daily genital swabs for HSV-2 DNA PCR for 28 days prior and after the third vaccination, and recorded the presence or absence of genital lesions daily.   Safety and immunogenicity were also monitored.

    Results:  310 participants received at least one vaccination and were evaluable. Compared to baseline, genital HSV-2 shedding was significantly reduced in all active vaccine groups, with highest reduction in the 60/75 µg dose group (55%, p<0.0001, Poisson model).  Shedding was also significantly reduced compared to placebo (p<0.0002 for all but 30/25 µg group). The magnitude of reduction in genital lesions paralleled changes in viral shedding for the active dose groups, with 60% reduction in the 60/75 µg group (p<0.0001 vs baseline, NS vs placebo). Vaccination was associated with moderate local and systemic reactogenicity that increased with MM dose, but <3% of participants discontinued vaccination because of adverse events. MM dose was not associated with increased rates of discontinuation.  No Grade 4 reactogenicity or related SAEs were seen.  Binding and neutralizing antibody titers were dose-related and highest in the 60/75 µg dose group.

    Conclusion: GEN-003 had significant antiviral activity, especially at the 60/75 µg dose, with acceptable safety profile.  Further study will assess longer term impact on viral shedding and lesions.

    Nicholas Van Wagoner, MD, PhD1, William Koltun, MD2, Gregg Lucksinger, MD3, Terri Warren, ANP4, Stephen Tyring, MD, PhD, FIDSA5, David Bernstein, MD, FIDSA6, Peter Leone, MD7, Lori Panther, MD, MPH8, Jacob Lalezari, MD9, Kenneth Fife, MD, PhD, FIDSA10, Richard Novak, MD11, Richard Beigi, MD, MSc.12, John Kriesel, MD13, Jason Chan, PhD14, Sybil Tasker, MD, FIDSA14, Seth Hetherington, MD14 and Anna Wald, MD, MPH, FIDSA15, (1)Infectious Diseases, The University of Alabama at Birmingham, Birmingahm, AL, (2)Medical Center for Clinical Research, San Diego, CA, (3)Tekton Research, Austin, TX, (4)Westover Heights Clinic, Portland, OR, (5)Center for Clinical Studies, Houston, TX, (6)Cincinnati Children's Hospital Medical Center, Cincinnati, OH, (7)University of North Carolina, Chapel Hill, NC, (8)Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, (9)Quest Clinical Research, San Francisco, CA, (10)Indiana University School of Medicine, Indianapolis, IN, (11)University of Illinois at Chicago, Chicago, IL, (12)OB Gyn, Magee Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, (13)University of Utah School of Medicine, Salt Lake City, UT, (14)Genocea Biosciences, Cambridge, MA, (15)Department of Medicine, University of Washington, Seattle, WA

    Disclosures:

    N. Van Wagoner, Genocea Biosciences: Investigator , Consulting fee and Research support

    W. Koltun, Genocea Biosciences: Investigator , Research support

    G. Lucksinger, Genocea Biosciences: Investigator , Research support

    T. Warren, Genocea Biosciences: Investigator , Research support
    Vical: Investigator , Research support
    GSK: Investigator , Research support
    Agenus: Investigator , Research support

    S. Tyring, Genocea Biosciences: Investigator , Research support

    D. Bernstein, Genocea Biosciences: Investigator , Research support

    P. Leone, Genocea Biosciences: Investigator , Consulting fee and Research support

    L. Panther, Genocea Biosciences: Investigator , Research support

    J. Lalezari, Genocea Biosciences: Investigator , Research support

    K. Fife, Genocea Biosciences: Investigator , Research support

    R. Novak, Genocea Biosciences: Investigator , Research support
    Merck: Investigator , Research support
    Gilead: Investigator , Research support
    GSK: Investigator , Research support
    Bavarian Nordic: Investigator , Research support

    R. Beigi, Genocea Biosciences: Investigator , Research support

    J. Kriesel, Genocea Biosciences: Investigator , Research support

    J. Chan, Genocea Biosciences: Employee , Salary

    S. Tasker, Genocea Biosciences: Employee , Salary

    S. Hetherington, Genocea Biosciences: Employee , Salary

    A. Wald, Agenus: Investigator , Research support
    Genocea: Investigator , Research support
    Vical: Investigator , Research support
    Gilead: Investigator , Research support
    Aicuris: Consultant , Consulting fee

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    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.