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HPTN 050
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.
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HPTN 050 paper
published!
The HPTN study paper was
published in the February 28 2006 issue of the
AIDS.
This paper provides the
results from the HPTN 050 study. The conclusion of the study is that a 2-week
course of 1% tenofovir vaginal gel used twice daily is well tolerated in
sexually abstinent and sexually active HIV-negative and HIV-positive women. The
PK results indicated that 14 of the 25 women who had PK sampling had low, but
detectable, serum tenofovir levels on either one or both (3 out of the 14) of
the sampling days. Expanded safety and effectiveness testing is warranted.
Please find the reference
for the paper below. Click
on the title to view the paper's abstract and to gain access to the full text
version on the AIDS website.
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 Feb 28; 20(4):543-51.
Protocol Status:
Concluded
Study
Summary
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
SDMC Protocol Specialist:
Karen Patterson
get info
Protocol Co-Chair:
Kenneth H. Mayer
get info
Protocol Co-Chair:
Lisa Maslankowski
get info
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