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

NCT01448616 | Completed Phase 4 Results DMC

• 1 other identifier: 41250
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

Conditions

Herpes Simplex Type II

Outcome Measures

Primary Outcomes (1)

• HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo

  The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.

  Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Secondary Outcomes (3)

• Within-person Changes in Log-copy Numbers of HSV

  Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

• Genital Lesion Rate

  Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

• Asymptomatic Shedding (Shedding on Days Without Genital Lesions)

  Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Study Arms (4)

Run-in Phase

NO INTERVENTION

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

Study Drug Phase: TDF

EXPERIMENTAL

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.

Drug: TDF; Drug: Placebo Vaginal Gel

Study Drug Phase: Vaginal TFV Gel

EXPERIMENTAL

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.

Drug: Vaginal TFV Gel; Drug: Placebo Tablets

Study Drug Phase: Double Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo Vaginal Gel; Drug: Placebo Tablets

Interventions

TDF 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.

Also known as: Tenofovir disoproxil fumarate (TDF) oral tablets

Study Drug Phase: TDF

Placebo Vaginal Gel 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.

Also known as: Placebo gel

Study Drug Phase: Double Placebo; Study Drug Phase: TDF

Vaginal TFV Gel 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.

Also known as: Tenofovir 1% Vaginal Gel

Study Drug Phase: Vaginal TFV Gel

Placebo Tablets 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.

Also known as: Oral placebo

Study Drug Phase: Double Placebo; Study Drug Phase: Vaginal TFV Gel

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead
• CONRAD: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

University of Washington Virology Research Clinic

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• 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.

  PMID: 26265463 DERIVED

• 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.

  PMID: 26044291 DERIVED

MeSH Terms

Interventions

Tenofovir; Vaginal Creams, Foams, and Jellies

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies

Limitations and Caveats

The study was not powered to detect differences in lesion rate; the study was appropriately powered to detect a 50% decrease in viral shedding only, and therefore may have been underpowered to detect significant findings for secondary outcomes.

Results Point of Contact

• Title: Rachel Bender Ignacio, MD MPH
• Organization: University of Washington

rbi13@uw.edu

2065204340

Study Officials

• Anna Wald, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 14, 2011
• First Posted: October 7, 2011
• Study Start: February 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 16, 2023
• Results First Posted: January 12, 2016

Record last verified: 2023-02

Locations

US (1)