Overview

This trial is active, not recruiting.

Condition herpes simplex type ii
Treatments tenofovir, placebo gel, tenofovir disoproxil fumarate (tdf), placebo tablets
Phase phase 4
Sponsor University of Washington
Collaborator CONRAD
Start date February 2012
End date June 2015
Trial size 55 participants
Trial identifier NCT01448616, 41250-A

Summary

The investigators propose a randomized, double blind, placebo-controlled, cross-over trial to evaluate the effect of oral and topical (vaginal gel) tenofovir on genital herpes simplex virus (HSV) shedding among herpes simplex virus type-2 (HSV-2) seropositive, human immunodeficiency virus (HIV) seronegative women. The investigators hypothesize that tenofovir will reduce genital HSV shedding compared to placebo.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(No Intervention)
Women will first participate in a run-in phase with twice daily swabbing.
(Experimental)
Participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.
tenofovir
Tenofovir 1% gel (w/w) is a gel formulation of tenofovir. Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.
placebo gel
Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects — negative or positive — on study endpoints.
tenofovir disoproxil fumarate (tdf)
Oral tenofovir will be administered as tablets. TDF (Viread®) tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.
placebo tablets
TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.

Primary Outcomes

Measure
HSV shedding
time frame: 9 weeks

Secondary Outcomes

Measure
within-person changes in copy numbers of HSV
time frame: 9 weeks
Average copy numbers of HSV
time frame: 9 weeks
Lesion rate
time frame: 9 weeks
Shedding on no lesion days
time frame: 9 weeks
Number of participants with adverse events (AEs) as a measure of safety and tolerability.
time frame: 9 weeks

Eligibility Criteria

Female participants from 18 years up to 50 years old.

Inclusion Criteria: - Women age 18-50 - HSV-2 seropositive by the University of Washington (UW) Western blot - History of recurrent genital herpes, with more than 4 recurrences but less than 10 in the last year or, if currently on suppressive therapy, with more than 4 recurrences but less than 10 in the year prior to starting suppressive therapy - HIV negative - General good health - Willing to not use antiviral therapy (other than the study drug) for the duration of the study - Willing to obtain a swab from genital secretions twice daily for the duration of the study - Willing to use effective birth control - Able to provide written informed consent at screening and enrollment Exclusion Criteria: - HIV positive or at high risk for HIV acquisition (intravenous drug user or HIV+ sex partner) - Hepatitis B (HepB) antigen (Ag) positive, or at high risk for HepB acquisition and not vaccinated - Have a history of adverse reaction to tenofovir and/or adefovir - Immunosuppressive medications, except for intranasal or topical (not high potency) steroids. - Any kidney disease, or renal insufficiency, defined as serum creatinine >1.5 mg/dl. Participants with a prior history of a single episode of pyelonephritis will be eligible. - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times upper limit of normal - Pregnancy, as confirmed by a urine pregnancy test, planning to become pregnant during the course of the trial, or breast-feeding. - Serious medical conditions or active infections - Any other conditions that in the judgment of the investigator would preclude successful completion of the clinical trial.

Additional Information

Official title Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial
Principal investigator Anna Wald, MD, MPH
Description The investigators propose a randomized, double-blind, placebo-controlled, cross-over study of 55 adult, healthy women who are HSV-2 seropositive and HIV-1 seronegative. Women will first participate in a run-in phase with twice daily swabbing. Following 4 weeks of swabbing, participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by University of Washington.