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1333
Therapeutic HSV-2 vaccine (GEN003) results in durable reduction in genital lesions at 1 year

Session: Oral Abstract Session: Clinical Trials
Saturday, October 11, 2014: 11:00 AM
Room: The Pennsylvania Convention Center: 109-AB
Background: Genital HSV-2 infection causes recurrent genital lesions and frequent viral shedding; current therapies do not completely control viral replication and require daily antiviral therapy.   The therapeutic vaccine GEN003 contains 2 HSV-2 proteins, gD and ICP4, and Matrix M2 adjuvant (MM) to promote both B and T cell immune responses. 

Methods: We conducted a randomized, placebo controlled clinical trial in which 143 participants with genital HSV-2 infection were randomized to receive 3 vaccinations with 10, 30 or 100 µg of GEN003 with or without MM, or placebo.    Participants collected twice daily swabs of genital secretions to assess genital shedding, and recorded genital lesions for 28 days prior to, immediately after; and 6 and 12 months after completion of vaccinations. Safety, immunogenicity and efficacy were monitored.

Results: Immediately after vaccination, viral shedding in the 30 µg and 100 µg with MM groups decreased from baseline (rate ratios [RR] 0.47 and 0.68, respectively; p<0.001 for both).  Shedding was unchanged from baseline for the placebo (RR= 1.01), unadjuvanted GEN003 (RR= 1.40), and 10 µg with MM groups (RR=1.01).  Shedding remained suppressed for the 30 µg with MM dose group at 6 months (RR=0.57; p<0.001).  Lesion rates were reduced after vaccination for the 30 and 100 µg with MM dose groups (RR 0.42 and 0.35, respectively; p<0.001 for both) and at 6 months for the 30 µg with MM dose (RR=0.26; p<0.001).  In a preliminary data review, at 12 months, lesion rates for the 30 µg with MM dose remained reduced (9.6% [n=29] at baseline versus 2.4% [n=17] at 12 months).  Three participants in the 10 µg with MM group discontinued dosing due to adverse events.  Injection reactions were previously reported (Wald, ICAAC 2013).  Other than reactogenicity, the number (%) of participants who reported 1 or more other Grade 3 or 4 AEs considered related to vaccination by treatment group were: 10 µg with MM, 3 (10%); 30 µg with MM, 2 (7%); 100 µg with MM, 1 (4%); GEN003 without adjuvant 1 (4%); Placebo, 0 (0%). 

Conclusion: The antiviral effect of GEN003 persisted for at least 6 months with an effect on genital lesions up to 12 months.  Immunotherapy with GEN003 may be an effective strategy, with or without traditional antiviral agents, to treat chronic genital HSV-2 infections.

Anna Wald, MD, MPH, FIDSA1, Terri Warren, ANP2, Kenneth Fife, MD, PhD3, Stephen Tyring, MD, PhD4, Patricia Lee, M.D.5, Nicholas Van Wagoner, MD, PhD6, David Bernstein, MD7, Jessica B. Flechtner, PhD8, Amalia Magaret, PhD9, Amy Morris10 and Seth Hetherington, M.D.8, (1)Department of Medicine, University of Washington, Seattle, WA, (2)Westover Heights Clinic, Portland, OR, (3)Indiana University School of Medicine, Indianapolis, IN, (4)Center for Clinical Studies, Houston, TX, (5)Center for Clinical Studies, Webster, TX, (6)Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (7)Cincinnati Children's Hospital Medical Center, Cincinnati, OH, (8)Genocea Biosciences, Cambridge, MA, (9)Departments of Laboratory Medicine and Biostatistics, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA, (10)IND2Results, Atlanta, GA

Disclosures:

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

T. Warren, Genocea: Investigator, Research support

K. Fife, Genocea: Grant Investigator, Grant recipient
Vical: Grant Investigator, Grant recipient

S. Tyring, Genocea: Investigator, Research support

P. Lee, None

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

D. Bernstein, Genocea: Research Contractor, Research support

J. B. Flechtner, Genocea Biosciences, Inc.: Employee, Salary and Stock options

A. Magaret, None

A. Morris, Genocea Biosciences, Inc.: Research Contractor, Consulting fee

S. Hetherington, Genocea Biosciences: Employee, Salary and stock options

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