VivaGel™ in Healthy Young Women
Condition: Herpes Simplex II
MeSH terms: Herpes Simplex
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety and tolerability of a medication applied
      vaginally twice daily in females versus placebo (inactive substance). Study participants will
      include 60 women, ages 18-24, non-pregnant, previously sexually active, Human
      Immunodeficiency Virus (HIV) negative and sexually transmitted infection (STI) free, in San
      Francisco or Kisuma, Kenya. Each study participant will be followed for 14 days of product
      use and an additional 7 days for safety assessments. Study procedures will include a physical
      exam with a pap smear, urine testing, blood sample testing, and a colposcopy (exam of the
      vagina and cervix using a lighted magnifying instrument). Information learned from this study
      may help to develop a safe and effective medication that could prevent herpes simplex virus
      and HIV. Participants may be involved in study related procedures for up to 55 days.
    

Detailed description: 
      Over half of global human immunodeficiency virus (HIV) infections occur among those aged
      18-24 years and young women are at a particularly high risk of acquiring genital herpes
      caused by herpes simplex virus type 2 (HSV-2) and other sexually transmitted infections
      (STI). This is a phase I, randomized, double blind, clinical trial of twice-daily vaginal
      VivaGel™ (n equals 40) versus placebo gel (n equals 20). The primary aim of this protocol is
      to test the safety and tolerability of VivaGel™ in young women, with the long-term aim of
      testing the efficacy of this compound in preventing HSV-2 in a future phase II/III trial. A
      total of 60 young women aged 18-24, non-pregnant, previously sexually active, STI and HIV
      free, in San Francisco and in Kisumu, Kenya will participate in this study. Eligibility
      screening will include medical history, pelvic exam with a Pap smear, urine pregnancy
      testing, HIV and STI counseling and testing, hematology testing and liver and renal function
      testing. Eligible participants will undergo a pelvic exam with colposcopy. Vaginal swabs will
      be collected to evaluate H2O2-producing lactobacilli and Gram stain, Chlamydia, gonorrhea,
      and prostate specific antigen (PSA) (to confirm lack of exposure to semen). Endocervical
      samples will be collected to measure immunological status. Blood will be collected to conduct
      hematology and liver and renal function testing, and plasma will be collected and stored for
      batch testing. Subjects will be provided with the investigational product or placebo, given a
      Daily Study Record, instructed how to use the product, complete the Daily Study Record, and
      report any adverse events (AEs). Follow-up visits will occur on Days 2, 7, 14, and 21. The
      primary study objective will be to determine the safety and tolerability of VivaGel™ applied
      vaginally twice daily for 14 days in HIV negative and STI-free young women. Safety
      assessments, comparing the VivaGel™ group to the placebo gel group, will include: incidence
      and severity of AEs, including genital tract signs and symptoms and mucosal changes as
      observed by colposcopy; vaginal microflora, including colonization with H2O2-producing
      lactobacilli; and laboratory parameters, including serum chemistry and hematology. The
      tolerability assessment, comparing the VivaGel™ group to the placebo gel group will include
      the proportion of participants who discontinued product use due to overt (i.e. observable)
      AEs, ascertained through a standardized questionnaire. The secondary objective of the study
      will be to report the effect of VivaGel™ applied vaginally twice daily for 14 days on the
      immune microenvironment in the lower genital tract of young women. Specifically, this will be
      tested by determining its effect on: the number and activation levels of endocervical immune
      cell populations; Secretory Leukocyte Protease Inhibitor (SLPI) levels; innate mucosal
      defenses, including local levels of cytokines in cervical secretions, and Toll-Like Receptor
      (TLR) expression by cervical immune cells; and the presence and expression levels of the HIV
      co-receptors CCR5 and CXCR4, and of their principal chemokine ligands by endocervical immune
      cells.
    

Intervention name(s): 3% w/w SPL7013 Gel; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Twice-daily vaginal application of 3.5 g of VivaGel™ (Carbopol®-based gel with 3% w/w SPL7013) in single use pre-filled applicators.; Placebo gel (Carbopol®-based formulation alone) in single use pre-filled applicators.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: VivaGel™, sexually transmitted, microbicide, herpes simplex