Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding

NCT ID: NCT01448616

Last Updated: 2023-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2015-06-30

Brief 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.

Detailed 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.

Conditions

Herpes Simplex Type II

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Run-in Phase

Women will first participate in a run-in phase with twice daily swabbing.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Study Drug Phase: TDF

Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.

Group Type: EXPERIMENTAL

TDF

Intervention Type: DRUG

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 Vaginal Gel

Intervention Type: DRUG

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.

Study Drug Phase: Vaginal TFV Gel

Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.

Group Type: EXPERIMENTAL

Vaginal TFV Gel

Intervention Type: DRUG

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 Tablets

Intervention Type: DRUG

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.

Study Drug Phase: Double Placebo

Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.

Group Type: PLACEBO_COMPARATOR

Placebo Vaginal Gel

Intervention Type: DRUG

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.

Placebo Tablets

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo Vaginal 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.

Intervention Type: DRUG

Vaginal TFV Gel

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Tenofovir disoproxil fumarate (TDF) oral tablets; Placebo gel; Tenofovir 1% Vaginal Gel; Oral placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

CONRAD

OTHER

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Anna Wald

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anna Wald, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington Virology Research Clinic

Seattle, Washington, United States

Countries

United States

References

Johnston C, Harrington R, Jain R, Schiffer J, Kiem HP, Woolfrey A. Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies. Biol Blood Marrow Transplant. 2016 Jan;22(1):149-56. doi: 10.1016/j.bbmt.2015.08.006. Epub 2015 Aug 8.

Reference Type: DERIVED

PMID: 26265463 (View on PubMed)

Bender Ignacio RA, Perti T, Magaret AS, Rajagopal S, Stevens CE, Huang ML, Selke S, Johnston C, Marrazzo J, Wald A. Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial. J Infect Dis. 2015 Dec 15;212(12):1949-56. doi: 10.1093/infdis/jiv317. Epub 2015 Jun 4.

Reference Type: DERIVED

PMID: 26044291 (View on PubMed)

Other Identifiers

41250

Identifier Type: -

Identifier Source: org_study_id