3 Grams Daily Valacyclovir in Chronic Hepatitis C Infection (Phase II)

The study is a randomized, double-blinded, placebo-controlled, Phase II clinical trial.
Participants will be recruited while attending regularly scheduled clinic appointments at
the Jackson VAMC. Baseline Visit. Participants will be randomized 1:1 in groups of 10 to
receive valacyclovir 1.5 gram orally twice daily or matching placebo. Enrolled participants
will complete 12 weeks of assigned therapy.

At the initial visit, participants will complete a short questionnaire detailing past
medical/social history and relevant symptoms. Venipuncture will be performed to obtain
samples for the laboratory tests. The baseline de-identified serum sample will be obtained
from the clinical lab and stored in research-approved freezer space for future confirmation
with the Biokit HSV-2 rapid assay. Follow-up visits will be scheduled at two-week intervals
after baseline. At each visit, pill-count, compliance and tolerability of medications will
be assessed using a short questionnaire. Venipuncture will be performed every four weeks
(i.e., at every other follow-up visit) to provide samples for the tests described below.
Information from each study visit will be recorded into the chart by the PI or RA and
entered into an encrypted database on a VA server. Laboratory Tests. HSV-2 infection will be
confirmed by performing the Biokit HSV-2 rapid assay on the baseline stored serum sample
using methods previously described in this proposal. Laboratory tests will include 1)
complete blood count, comprehensive metabolic profile, and quantitative HCV RNA; and 2)
Focus HerpeSelect HSV-1 IgG for participants who were seronegative for HSV-1 at baseline.
Patients IL28-B genotype will also be assessed at baseline. The PI will review all
laboratory parameters.

Baseline characteristics between the groups will be compared using appropriate parametric
tests. Analysis will be intention to treat with the inclusion of all subjects who were
randomized to drug or placebo. The primary outcome is change in HCV viral load in the
treatment group compared with placebo. Because we are expecting a 0.5 log10 decline in HCV
viral load, we will use one-sided parametric tests. All viral loads will be
log10-transformed before analysis. We anticipate using a higher cut-off will eliminate false
positive HerpeSelect HSV-2 IgG assays.

Inclusion Criteria:

- Documentation of chronic HCV infection with genotype testing and previous positive
HerpeSelect HSV-2 IgG assay

Exclusion Criteria:

- Antiherpes or immunomodulatory therapy during the past 30 days

- HIV or chronic hepatitis B infection

- Decompensated liver disease (ascites, hepatic encephalopathy, coagulopathy,
jaundice/icterus)

- Creatinine clearance <50 ml/min

- Female subject who is pregnant or nursing

- Gastrointestinal disorder which might result in malabsorption of valacyclovir

- History of erythema multiforme major, thrombotic thrombocytopenia purpura or
hemolytic uremic syndrome

- Therapy for hepatitis C in the previous 6 months