VALTREX(Valacyclovir) Once Daily for Viral Shedding In Subjects Newly Diagnosed With HSV-2

Study Overview
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Brief Summary
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Eligible subjects will be randomized to receive VALTREX 1g or placebo once daily for 60 days in a two-way crossover study with a washout period of 7 days in between.

Official Title
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The Effect of Valacyclovir 1g Once Daily on HSV-2 Viral Shedding in Subjects Newly Diagnosed With Genital Herpes Infection

Conditions
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Herpes Labialis

Intervention / Treatment
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* Drug: valacyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is in overall general good health. If female, subject must be of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal or surgically sterile); or Childbearing potential, but must have a negative pregnancy test at randomization, and must be compliant with one of the following: Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period of 1 week after study completion or premature discontinuation from the study (to account for elimination of the drug); Have a male partner who is confirmed to be sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; Use of contraceptive(s) with a documented failure rate of less than 1% per year, including but not limited to: implants of levonorgestrel, use of injectable progestogen, oral contraceptives (either combined or progestogen only), an intrauterine device (IUD) or spermicide plus a mechanical barrier (condom/diaphragm). Subjects must be newly diagnosed with a first recognized episode of genital herpes as described in (a) or (b) below (See Appendix 3): a.HSV-2 seropositive at screen, with documented clinical signs and symptoms consistent with genital herpes at screen or within 4 months prior to randomization or b.HSV-2 seronegative at screen, AND HSV-2 culture positive or HSV-2 PCR positive with documented clinical signs and symptoms consistent with genital herpes at screen or within 4 months prior to randomization. Subject must be willing and able to provide written informed consent and comply with the protocol. Exclusion Criteria: Subject is known or suspected to be immunocompromised (e.g., subjects receiving immunosuppressive therapy or chemotherapy for malignancy, or are seropositive for HIV). Subject received an investigational drug in the 30 days prior to the randomization visit. Subject is receiving systemic antiviral or immunomodulatory treatments. Subjects who have received systemic antiherpetic treatments (e.g., valacyclovir, acyclovir, ganciclovir, famciclovir) within 3 days of starting study drug, or immunomodulatory treatments in the 30 days before starting study drug. Subject has clinically significantly impaired renal function as defined by creatinine clearance less than 50ml/min (calculated using the Cockcroft-Gault formula). Subjects with a history or evidence of decompensated liver disease, or clinically significantly impaired hepatic function defined as an ALT (alanine transaminase) level >3 times the normal upper limit. Subject is known to be hypersensitive to valacyclovir, acyclovir, ganciclovir or famciclovir. Subject has malabsorption or vomiting syndrome or other gastrointestinal dysfunction that may impair drug pharmacokinetics. Female subject who is contemplating pregnancy within the duration of the study drug dosing period. Female subject who is pregnant and/or nursing. Subject with current alcohol or drug abuse. Subjects who have received suppressive (daily) therapy for genital herpes prior to randomization. Suppressive therapy is defined as daily antiherpetic therapy of at least 4 weeks duration. Subjects with a history of ocular HSV (herpes simplex virus) infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: valacyclovir|valacyclovir|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Days of Total Shedding (Clinical and Subclinical) as Determined by Type-specific Polymerase Chain Reaction (PCR) Assay for Herpes Simplex Virus Type 2 (HSV-2) | Each participant's study day were classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab are positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Percent of days with HSV-2 shedding was defined for each participant as the percent of days with PCR data for which HSV-2 shedding was detected by a positive PCR result, i.e., the number of days with HSV-2 PCR shedding divided by total number of days with PCR data, multiplied by 100. Sum of the percent clinical and nonclinical shedding days was reported as total shedding. Mean percent of days with HSV-2 shedding was reported for each treatment group. | Up to 60 days in each treatment period (Up to 148 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Days Subclinical Shedding (no Genital Lesions Present) | The percent of days with subclinical HSV-2 shedding was defined as the percent of all days with PCR data for which subclinical HSV-2 shedding was detected (shedding in the absence of a genital lesion). Mean percent of days with subclinical HSV-2 shedding was reported for each treatment group. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. | Up to 60 days in each treatment period (Up to 148 days) | 
| Mean Percent Days Clinical Shedding (Presence of Genital Lesions) | The percent of days with clinical HSV-2 shedding was defined as the percent of all days with PCR data for which clinical HSV-2 shedding was detected (shedding in the presence of a genital lesion). Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with clinical HSV-2 shedding was reported for each treatment group. | Up to 60 days in each treatment period (Up to 148 days) | 
| Percentage of Participants With no Shedding | The proportion of participants with no shedding was defined as the number of participants with no HSV-2 shedding detected by PCR divided by the total number of participants with PCR data in the Treatment Period. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with no shedding was reported for each treatment group. | Up to 60 days in each treatment period (Up to 148 days) | 
| Percentage of Participants With at Least One Genital Herpes Recurrence | The proportion of participants with at least one genital herpes recurrence was defined as the number of participants with at least one investigator-confirmed genital herpes recurrence divided by the total number of participants with at least one clinic visit in the treatment period. | Up to 60 days in each treatment period (Up to 148 days) | 
| Median Time to First Genital Herpes Recurrence (Days) | Time to first genital herpes recurrence was evaluated using Kaplan-Meier estimates of investigator-confirmed genital herpes recurrences censoring the data from participants who prematurely discontinue the study at the time of discontinuation. | Up to Day 68 | 
| Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE) | AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include adverse events that result in death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. No SAEs were reported in this study. | Up to 148 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Genital Herpes