Phase I Safety and Acceptability Study of the Vaginal Microbicide Agent PMPA Gel
What is HPTN 050?
Potential approaches to the development of topical agents for the prevention of vaginal HIV transmission include products that block initial virus infection through broad-based microbicidal activity or through inhibition of virus-cell attachment. However, it is unlikely that any single product will be completely efficacious in preventing initial HIV infection. Thus, the development of a topical product that could block local virus replication once infection has occurred is needed. Topical PMPA gel was chosen for study because of (1) activity in potential target cells of the vagina and cervix; (2) its effectiveness in preventing the establishment of systemic infection in the SIV- macaque model; (3) demonstrated inhibition of vaginal transmission of SIV in the macaque model; and (4) an expectation of low local and systemic toxicity.
HPTN 050 is a multi-site Phase I stepped, parallel dose and frequency study of PMPA gel (and carrier vehicle if required) to be conducted among up to 96 women and their male sexual partners (when relevant) from three cites in the US: New York, NY; Philadelphia, PA; and Providence, RI. All participants will apply PMPA gel intravaginally for 14 consecutive intramenstrual days.
The dose and frequency of application will be escalated across “cohorts” of up to 12 study participants each. Participants in cohorts assigned to once daily dosing will apply the dose at bedtime. Participants assigned to twice daily dosing will apply one dose in the morning and the other at bedtime. Two cohorts, HIV uninfected, sexually active and partners and HIV infected, sexually active and partners, will substitute a coital dose at least two hours before vaginal sexual intercourse for either the morning or bedtime dose on at least two days per week during the study dosing period.
Protocol Status: Concluded
Study Purpose: To determine the safety and acceptability of PMPA gel for vaginal use among sexually abstinent and sexually active HIV-uninfected, and HIV-infected women; and to determine the acceptability of PMPA gel among their male sexual partners (when relevant).
Study Design: Phase I multisite stepped parallel dose and frequency study with 14 days of product exposure and up to 21 days of follow-up for each female participant.
Study Population: Up to 72 HIV-uninfected women (up to 60 sexually abstinent and up to 12 sexually active), up to 24 HIV-infected women (up to 12 sexually abstinent and up to 12 sexually active) and up to 24 male sexual partners (12 HIV-uninfected and 12 HIV-infected)
Study Size: Up to 96 women and up to 24 men will be enrolled
Study Duration: Accrual will require 11 months. Each participant will be followed for up to 21 days. Acceptability interviews will be convened within four weeks after the completion of product use and follow-up. Therefore the entire study should be completed within 13 months.
Treatment Regimen: Female participants in cohorts A – D will apply PMPA gel intravaginally for 14 intramenstrual days and participants in cohort V (if required) will apply vehicle only as follows: (see protocol for regimen table)
Primary Objectives: To assess the safety and toxicity of PMPA gel for vaginal use in assigned doses and frequency on vulvar and cervicovaginal mucosa in HIV-uninfected women at low risk for HIV infection as well as in HIV-infected women. To assess the systemic safety and absorption of PMPA gel for vaginal use in low-risk, HIV uninfected women as well as in HIV infected women.
Secondary Objectives: To assess the acceptability of, and adherence to, a short-term regimen of PMPA gel for vaginal use in low-risk, HIV-uninfected women as well as in HIV infected women and their male sexual partners (when relevant). To examine qualitative aspects of acceptability and adherence as a pilot for substantive qualitative and quantitative assessments in future studies. Exploratory Objectives:To measure the occurrence of vaginal shedding of HIV before and after use of PMPA gel for vaginal use. To assess the genotypic resistance patterns of HIV in genital secretions and blood samples from the HIV-infected female participants of the course of PMPA vaginal gel use. To measure changes in vaginal flora before and after use of PMPA gel for vaginal use using the Nugent Scoring System
HPTN 050 Publications
Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006, 20: 543-51 PMID: 16470118
Carballo-Diéguez A, Balán IC, Morrow K, Rosen R, Mantell JE, Gai F, Hoffman S, Maslankowski L, El-Sadr W, Mayer K. Acceptability of tenofovir gel as a vaginal microbicide by US male participants in a Phase I clinical trial (HPTN 050). AIDS Care. 2007, 19: 1026-31 PMID: 17852000