Randomized Trial to Evaluate Suppressive Effect of High-Dose Valacyclovir Versus Once-Daily Valacyclovir on Persons With HSV-2

A Randomized, Cross-Over Study to Evaluate the Suppressive Effect of High-Dose Valacyclovir Versus Once Daily Valacyclovir on Herpes Simplex Virus Type 2 Genital Shedding in Herpes Simplex Virus-2 Seropositive Adults

On 13 August 2008, this trial was submitted to ClinicalTrials.gov as modification to NCT00362297. On 28 April 2011, the two records were split for administrative purposes and each trial was given its own unique study record. Please refer to the "History of Changes" on posting NCT00362297 for a detailed summary of the modifications.

The purpose of the research study is to evaluate the effectiveness of high-dose valacyclovir compared to once daily valacyclovir for reduction of asymptomatic HSV-2 genital shedding in persons with genital herpes.

The study will enroll men and women who are 18 years or older, test positive to HSV-2 (by blood test) and have had a first outbreak of HSV-2 within the past 6 months or have had at least 4 genital herpes outbreaks in the past year. Participants must be HIV negative and willing to stop taking suppressive therapy for HSV for the one week wash out period. (Females only: You must not be pregnant or breast-feeding). Both men and women will be asked to use an effective form of birth control.

Involvement in the study will last 11-weeks and you will be asked to visit the clinic every 2-weeks. At each visit, you will be given medication to take daily (either once daily valacyclovir or high dose valacyclovir; you will receive both medications at some point during this study). We will ask you to give a blood sample for liver, kidney and blood count testing at each visit. There will be a total of 8 study visits and each visit will last approximately 30 minutes. We will ask that you complete a daily symptom diary and collected daily home swabs 4-times a day, everyday during the study. Each daily home swab will take less than 3 minutes to perform.

Screening Assessment

Patients will be assessed for their eligibility to enter the study at a screening visit. After signing informed consent they will undergo a medical history and the following information will be recorded in the Case Report Form (CRF):

• Demographic Data: Date of birth, sex, marital status, education and race
• Previous antiviral medication taken
• History of sexually transmitted infections and sexual history.
• Women of childbearing potential will undergo a urine pregnancy test. Serologic samples for HSV-2 and HIV will be obtained. Part of the blood sample will also be used for safety labs.

Start of Study Visit (Day 0) and Day 14, 28, 35, 42, 56, 70, and 77 Follow-Up Visits.

Eligible patients will return to clinic to be given study drug and a patient diary card on which to record concomitant medications, signs and symptoms, and adverse experiences. The investigator will instruct the patient on daily home viral sample collection, taking the study drug, and completing the diary card. The patient will be instructed to return to clinic in 2 weeks, +/- 2 days. Medication compliance will be assessed at each visit using pill counts. Safety labs will be performed on day 14, 28, 35, 56, 70 and 77.

Crossover Study Visit Prior To Washout Period (Day 35-41)

Participants will not be given study drug or placebo during the 7-day washout period. Participants will not be required to obtain swabs during the washout period.

Daily Home Viral Sample Collection

Participants will collect swabs from the genital mucosa four times per day and store the samples in PCR media with preprinted labels. Women will swab the cervicovaginal, vulvar and perianal areas, and men will swab the penile and perianal. Every two weeks, they will return the samples to the Virology Research Clinic when they present for additional study drug and assessment.

Final Study Visit (Day 77)

At the final study visit at Day 77 or for premature discontinuation, the investigator will perform the activities at the regular study visits, with the exception of the dispensation of study drug.

Inclusion Criteria:

• 18 years or older;
• HSV-2 seropositive by Western Blot;
• not receiving any drugs with known anti-HSV-2 activity for study duration;
• history of primary genital herpes infection within past 6 months OR history of 4 or more HSV recurrences per year during the past year OR 4 or more recurrences per year prior to initiation of suppressive antiviral therapy; or shedding HSV-2 from genital mucosa on >25% of days in shedding session performed at the VRC within the last 2 years.
• able to comply with the study protocol;
• women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;
• women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;
• in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;
• planning to remain resident in the area of the study center for the duration of the study participation;
• HIV seronegative.

Exclusion Criteria:

• hypersensitivity to acyclovir or valacyclovir;
• pregnant women;
• HIV positive or other immunosuppressed state, including chronic steroid use. Intermittent nasal or topical steroids are acceptable