MTN-017: Phase II Safety and Acceptability Study of Tenofovir Gel Reformulated for Rectal Use

Published: January 11, 2012

Summary
·     MTN-017 is a Phase II study to find out whether a reformulated version of vaginal tenofovir gel is safe and acceptable as a rectal microbicide. The study will enroll approximately 216 men who have sex with men at trial sites in South Africa, Peru, Thailand and the United States. Results of MTN-017 will help determine whether further testing can be conducted to determine if the gel can help prevent the transmission of HIV through anal sex.
 
·     MTN-017 is a study of the Microbicide Trials Network (MTN), a clinical trials network established and funded in 2006 by the Division of AIDS at the National Institute of Allergy and Infectious Diseases with co-funding from the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of the U.S. National Institutes of Health. Leading the study are Ross Cranston, M.D., F.R.C.P., of the University of Pittsburgh, and Javier R. Lama, M.D., M.P.H, of IMPACTA PERU Clinical Trials Unit in Lima, Peru.
 
·     Tenofovir gel was developed as a microbicide to prevent HIV infection through vaginal sex. Two trials of tenofovir vaginal gel have produced conflicting results, while a third trial is ongoing. The gel being evaluated in MTN-017 is a version of tenofovir gel reformulated for rectal use.
 
·     As the first Phase II trial of a rectal microbicide, MTN-017 is part of a research agenda at the MTN focused on the development of HIV prevention products for men and women who engage in anal sex, a major risk factor for HIV.
 
Why this Study is Important
Microbicides are products being developed to prevent or reduce the sexual transmission of HIV or other sexually transmitted infections when applied inside the vagina or rectum. Products currently being tested in clinical trials contain antiretroviral (ARV) drugs, many of which are commonly used to treat people with HIV. Although the majority of microbicide research has focused on products to prevent HIV through vaginal sex, research addressing the need for rectal microbicides is gaining momentum. Anal sex is a common practice by both men and women around the world. According to some estimates, the risk of becoming infected with HIV during anal sex is 20 times greater than vaginal sex because the rectal lining is thinner and more fragile than the vaginal lining.
 
As an important first step to the development of rectal microbicides, researchers have been exploring whether microbicides originally formulated as vaginal gels are safe and effective to use in the rectum. One such product is tenofovir gel, which was found safe and 39 percent effective in reducing the risk of HIV in women who used it before and after vaginal sex in a study called CAPRISA 004. More recently, however, researchers conducting MTN’s VOICE Study closed the tenofovir gel arm of the trial after a routine review of study data determined that daily use of the gel, while safe, was not effective in preventing HIV among the women who used it vaginally. While it won’t be possible to understand why tenofovir gel was not effective in VOICE until after the study is completed and the data fully analyzed in late 2012 or early 2013, FACTS 001, a Phase III trial testing the same regimen of tenofovir gel used in CAPRISA 004, is continuing to enroll women at trial sites in South Africa.
 
MTN researchers also have been conducting studies of tenofovir gel as a rectal microbicide. Unlike CAPRISA 004, VOICE and FACTS 001, this research is focused on a different population of high-risk individuals who acquire HIV through anal sex rather than vaginal sex. Because tenofovir gel may work differently against HIV in rectal tissue, researchers want to learn whether it is safe to use rectally and can reduce the risk of HIV through anal sex.
 
The gel that will be evaluated in MTN-017 is not the vaginal formulation of tenofovir gel used in the effectiveness studies involving women. It is a reformulated version in response to results of RMP-02/MTN-006, which found that the vaginal gel generally safe, but caused gastrointestinal side effects in a few participants. To make it more amenable for rectal use, researchers reduced its glycerin content and tested it in a Phase I safety study called MTN-007, whose results are expected in early 2012. MTN-017 is a larger follow-up study to MTN-007 that will further explore adherence to and safety of the reformulated gel. 
 
How the Study is Designed
MTN-017 is a Phase II trial designed to evaluate the drug absorption, participant acceptability and safety of a rectal-specific formulation of tenofovir gel used daily and used before and after sex, as well as daily use of an oral tablet called Truvada®. The study plans to enroll approximately 216 HIV-negative men who have sex with men. (Transgendered men and women will not be included in MTN-017, but MTN is planning to study rectal microbicides in this population in a separate study.) Each participant will follow all of the study regimens (rectal tenofovir gel used daily; rectal tenofovir gel used before and after sex; and Truvada tablets taken daily) for eight weeks, with a weeklong break between regimens when no product will be used. The order in which participants will follow the study regimens will be based on random assignment. During the course of the study, participants also will receive ongoing HIV risk reduction counseling, free condoms and be tested regularly for HIV.
 
The tests and procedures performed as part of the study will determine how much drug is absorbed in blood, rectal fluid and tissue, and assess whether use of the products causes changes in cells or tissue. To explore the acceptability of the gel, study participants will be asked about any side effects they may have experienced, their likes and dislikes about using the gel either daily or with sex, and whether they would consider using it in the future.
 
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