Biological Efficacy Study of HerpV Vaccine With QS-21 to Treat Subjects With Recurrent Genital Herpes

The purpose of this study is to evaluate the effect the HerpV vaccine has on recurring episodes of genital herpes by evaluating viral shedding before, after treatment.

This study will evaluate the biological effectiveness and safety of the HerpV vaccine in combination with adjuvant QS-21. The Safety and tolerability of HerpV plus QS-21 will also be evaluated by collecting number and severity of adverse events throughout the study.

Biological effectiveness will be evaluated by comparing the viral shedding rate during the treatment period as compared to the baseline period of the study.

Subjects will undergo a baseline/ screening period. This is a 45 day period when the subject collects a swab of the genital area each day. . In case of a recurrence, subjects will be required to collect two swabs a day. If the subject collects at least 80% of the swabbing samples and meets all eligibility criteria they may enroll in the study.

Subjects who meet all inclusion and no exclusion criteria will be enrolled and randomized in Study Period 1 (treatment period). In order to assure the trial enrolls a good representation of women and men, a prespecified cap on women will be set at 50 (approximately 67% of the total enrolled population.)

Study Period 1 consists of three treatments and a 45 day swabbing period after the last treatment. The subject will collect swabs of the genital region each day for 45 days.

Subjects who successfully complete Study Period 1 will proceed to Study Period 2. They will receive a booster injection of study drug or placebo according to their orginal randomization assignment. The subjects will again enter a 45 day swabbing period, collecting swabs of the genital area each day for 45 days.

To evaluate immunologic response subjects will be required to have blood drawn at various time points through out the study.

Subjects will be required to suspend suppressive antiviral therapy for the duration of the study (up to week 48).

For one week before and during each 45 day swabbing period subjects will also be required to suspend episodic antiviral therapy.

• Drug: HerpV and QS-21
  HerpV (formerly AG-707 rh-Hsc70 Polyvalent Peptide Complex) in combination with adjuvant QS-21.
  Other Name: AG-707
• Drug: Placebo
  phosphate buffered saline.

• Experimental: HerpV and QS-21
  HerpV and QS-21
  Intervention: Drug: HerpV and QS-21
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Seropositive for HSV-2
• Clinically active genital herpes defined as a history of 1-9 episodes per year for at least one year prior to screening or one year prior to beginning suppressive therapy.
• Willing to either use an effective method of contraception or abstain from sexual intercourse throughout the 48 week study period.
• If female of childbearing potential, have a negative serum pregnancy test.
• Agree to not receive any other investigational drugs while enrolled in this study.
• The above criteria must be met before subjects are allowed to enter the 45 day swabbing period to be screen for the study.
• Completion of greater than or equal to 80% (36 days) of the 45 day consecutive daily genital swabs.

Exclusion Criteria:

• Severe active infection, compromised cardiopulmonary function, or other serious medical illness that, in the opinion of the Principal Investigator, would prevent study completion.
• A history of HSV infection of the eye (herpes simplex interstitial keratitis or uveitis), or herpes-associated erythema multiforme.
• A history of immune suppression or autoimmune disorder.
• Continued use of suppressive anti-viral therapy for HSV-2; a one week washout of any anti-viral therapy (suppressive and episodic) is required prior to initiating the swabbing period.
• Concomitant use of systemic corticosteroids or immune-suppressive medications. The use of nasal steroids is acceptable.
• HIV positive.
• Presence of active Hepatitis B or C infection.
• Known hypersensitivity or allergies to acyclovir or valacyclovir.
• Pregnant or breast-feeding women.