Fact Sheet Ongoing and Planned Trials of the MTN
Fast Facts
· The Microbicide Trials Network (MTN) portfolio of clinical trials is considered among the most critically important for advancing the field of HIV prevention. Much of its emphasis is on the evaluation of antiretroviral (ARV)-based prevention strategies, looking at whether some of the same ARVs commonly used to treat HIV can also be used for prevention, as either a vaginal microbicide or an oral tablet, an approach called pre-exposure prophylaxis (PrEP).
· MTN researchers have been conducting the only studies involving the use of HIV prevention products during pregnancy and breastfeeding to understand their safety in both women and their babies. These studies are critical because women need a product that will be safe and effective to use in all stages of life, including during pregnancy, a time when the risk of acquiring HIV from an infected partner is particularly high.
· Anal sex is common among men who have sex with men, and practiced by women around the world, yet the risk of acquiring HIV through unprotected anal sex is at least 20 times greater than with vaginal sex. The MTN is making significant contributions in the area of rectal microbicide research, leading studies that are important steps toward developing a product to protect against HIV transmitted through receptive anal intercourse.
· In addition to microbicides in the form of a gel, the MTN is exploring other types of formulations, including vaginal rings. Unlike a vaginal gel that is used every day or at the time of sex, rings under study are inserted monthly and release the active ingredient slowly over time so that feasibly a woman would have long-lasting protection against HIV. MTN plans to conduct the first-ever Phase III trial of a vaginal ring.
Ongoing and Planned Trials
MTN-003 –VOICE – Vaginal and Oral Interventions to Control the Epidemic – is a major HIV prevention trial designed to evaluate the safety and effectiveness of two different ARV-based approaches for preventing sexual transmission of HIV in women: daily use of an ARV tablet (tenofovir or Truvada) or daily use of an ARV-based vaginal gel (tenofovir gel). The study began in September 2009 and enrolled 5,029 women in Uganda, South Africa and Zimbabwe. Researchers stopped testing tenofovir tablets after an independent review of study data in September 2011 concluded that although the tablets were safe they were no more effective than placebo in preventing HIV. A November 2011 routine review drew the same conclusions about tenofovir gel, finding it safe but not effective among the women in the study. VOICE continues to evaluate Truvada. Final results, due in early 2013, will determine whether its daily use is safe and effective in preventing HIV in the women who remain in the study as well as help to understand why the tenofovir tablets and tenofovir gel were not.
MTN-003B (VOICE B) – The Bone Mineral Density Sub-study is an observational study in a subset of participants in VOICE that is exploring the potential effects, if any, that daily use of oral ARVs may have on bone health in HIV-negative women, and in particular, pre-menopausal women in Africa.
MTN-003C (VOICE C) – Also known as the Community and Adherence Sub-study, VOICE C aims to identify specific factors within a participant’s household, social environs or broader community that can influence her ability and willingness to follow the daily regimens being tested in VOICE – taking an oral tablet or applying a vaginal gel.
MTN-005 – An expanded safety and acceptability study of a non-medicated vaginal ring made of a silicone elastomer in 252 sexually active, HIV-negative women. The study is being conducted at three sites – one in India and two in the United States – in collaboration with the Population Council.
MTN-007 – A Phase I study designed to determine if rectal use of a reformulated version of tenofovir gel is safe and whether men and women would be willing to use it as a rectal microbicide. The study, which is a follow-up study to RMP-02/MTN-006, involved 60 participants at three U.S. sites. Results are anticipated to be reported in early 2012.
MTN-008 – A Phase II expanded safety and drug absorption study of tenofovir gel used daily in women who are in their third trimester of pregnancy, and women who are breastfeeding. As planned, the study will involve 90 pregnant women – 45 women at 37 weeks gestation and 45 women at 34 weeks gestation, who will use tenofovir gel daily for seven consecutive days; and 15 women who are breastfeeding, who will use gel for seven days. MTN-008 is a follow-up study to MTN-002 and ongoing at two U.S. sites.
MTN-009 – Also called the HIV Drug Resistance Study, the aim of MTN-009 is to provide a reliable assessment of the prevalence of HIV drug resistance in a representative population of women from KwaZulu-Natal, South Africa, where a woman’s HIV risk is among the highest, and to understand if certain risk behaviors are associated with resistance. The study has been completed and results are anticipated in early 2012.
MTN-011 – A Phase I study that aims to determine the effect that vaginal intercourse may have on drug absorption and drug activity of tenofovir gel. The study will enroll approximately 40 couples at two U.S. sites. Results are expected to provide insight into dosing regimens of tenofovir gel around intercourse.
MTN-012/IPM 010 – A Phase I study that assessed the safety and tolerance of a vaginal microbicide containing the ARV drug dapivirine when applied topically to the penis of sexually abstinent men. The study was conducted in collaboration with the International Partnership for Microbicides. Results are due mid-2012.
MTN-013/IPM 026 – A Phase I safety and drug absorption study testing 28-day use of a vaginal ring containing either dapivirine, maraviroc or the two ARVs combined. The study is the first clinical trial of a vaginal ring containing maraviroc, and the first to test a vaginal ring with two active drugs. It is being conducted at three U.S. sites in collaboration with the International Partnership for Microbicides.
MTN-014 - A Phase II study that intends to examine drug absorption patterns in both rectal and vaginal tissue when tenofovir gel is applied either vaginally or rectally. The study, which is in development, will involve women at two sites – one in the U.S. and one in South Africa.
MTN-015 – A long-term, observational study that seeks to understand the nature of HIV progression and treatment response in HIV-positive women who become infected while in a HIV prevention trial of either a topical microbicide or oral PrEP. The study will help better understand the impact of these agents on the natural history and clinical course of HIV and the prevalence and patterns of HIV drug resistance over time.
MTN-016 –EMBRACE –Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure –seeks to learn whether using a vaginal microbicide or ARV tablets for HIV prevention can affect a woman’s pregnancy outcome or her baby’s general growth and development. The study involves the creation of a database of health information from women who either unintentionally became pregnant while in an HIV prevention trial or who participated in a safety study of microbicides during pregnancy. Health information about the babies born to these women will also be included.
MTN-017 – A Phase II safety and adherence study of a rectal formulation of tenofovir gel used daily and before and after sex, and oral Truvada. As currently planned, the study will include approximately 216 men who have sex with men who will follow each of the regimens for eight weeks. The study, which is in development, will be conducted at sites in the U.S., Peru, South Africa and Thailand.
MTN-018 - CHOICE - Committed to Having Options for Interventions to Control the Epidemic, is a follow-up open-label study to VOICE, which was designed to move forward if VOICE were to find any of the products safe and effective. Based on two interim reviews of study data, VOICE has already determined that tenofovir gel and tenofovir tablets were not effective among the women in the study. If the results of VOICE indicate that Truvada is safe and effective, all former participants who are HIV-negative will be invited to join and have access to the study product during the one-year study. Women who are pregnant, or intend to become pregnant, or are breastfeeding, will be able to participate in sub-studies of CHOICE that plan to investigate product safety among pregnant (CHOICE C) and breastfeeding women (CHOICE B). If implemented, CHOICE will help to inform the broader implementation of oral PrEP and be important for understanding the overall safety of this approach in healthy women of reproductive age.
MTN-019 – A randomized placebo-controlled Phase II extended safety study of tenofovir gel used daily in the second and third trimesters of pregnancy that had been in development but is now on hold for an indefinite period of time
MTN-020 – ASPIRE - A Study to Prevent Infection with a Ring for Extended Use - is a Phase III effectiveness study of a vaginal ring containing the antiretroviral dapivirine that is expected to be launched at several sites in Africa beginning mid- 2012. About 3,476 women will be enrolled, who will be randomly assigned to insert either the dapivirine ring or a placebo ring every four weeks for at least one year. The dapivirine vaginal ring was developed by the International Partnership for Microbicides. ASPIRE is the first Phase III trial of a vaginal ring for preventing HIV.
MTN-021 - A Phase II expanded safety and tolerability study of tenofovir gel used daily for 12 weeks in adolescent girls ages 15-18 in the U.S. that was to be conducted in collaboration with the Adolescent Medicine Trials Network for HIV/AIDS Interventions of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study has been placed on hold for an indefinite period of time.
Recently Completed Trials
MTN-001 – A Phase II trial that was the first study to make head-to-head comparisons between tenofovir gel and oral tenofovir, looking at differences in drug absorption in blood and vaginal tissue as well as women’s preferences for each daily regimen. The study involved 144 women, evenly divided between the U.S., and Uganda and South Africa, who used each product daily for six weeks, as well as the two together. The study found that most women in the U.S. favored the tablet, while African women favored the gel and tablet equally. Daily use of the vaginal gel achieved a more than 100-times higher concentration of active drug in vaginal tissue than did the oral tablet, while, compared to the gel, the tablet used daily was associated with a more than 20-times higher active drug concentration in blood. Results were reported in February 2011.
MTN-002 – The first study of a candidate topical microbicide ever to be conducted in pregnant women, MTN-002 sought to understand if and to what extent pregnancy affects how the body absorbs the active drug in a gel and whether the drug can be transferred to the fetus. The Phase I study involved giving a single dose of tenofovir gel to 16 healthy, HIV-uninfected women hours before they gave birth by scheduled Cesarean section. Results, which were reported in May 2010, found that only small amounts of drug were absorbed into the mother’s bloodstream, amniotic fluid and umbilical cord (fetal) blood. There were no serious side effects attributed to the gel in either the mothers or their newborns.
MTN-004 – A Phase I study that evaluated the safety, acceptability and ease of use of the microbicide candidate VivaGel® (SPL7013 Gel) in sexually active, HIV-negative women ages 18 to 24. The study, a collaboration with NIAID’s Adolescent Medicine Trials Network for HIV/AIDS Interventions, was conducted at two U.S. sites and one in Puerto Rico. Results, reported in May 2010, found that VivaGel was generally well tolerated but less acceptable to use than the two placebo gels studied, suggesting that it may be necessary to consider reformulating VivaGel before moving to further studies.
RMP-02/MTN-006 – A Phase I study involving 18 HIV-negative men and women that was designed to determine whether the vaginal formulation of tenofovir gel is safe to use in the rectum, and through novel laboratory studies, if the gel prevents HIV infection in rectal tissue sampled from study participants. Results, which were reported in February 2011, found that HIV infection was significantly inhibited in rectal tissue sampled from participants who used tenofovir gel daily for one week compared to tissue from those who used a placebo gel. Only 25 percent of participants who used tenofovir gel said they liked it. The majority of participants experienced only minor side effects, however a few experienced severe gastrointestinal side effects. Researchers have since reformulated the gel to make it more acceptable for rectal use. RMP-02/MTN-006 was conducted in collaboration with the NIAID Division of AIDS Integrated Pre-Clinical/Clinical Program for HIV Topical Microbicides.
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The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners who are devoted to reducing the sexual transmission of HIV through the development and evaluation of products applied topically to mucosal surfaces or administered orally. More information about the MTN is available at www.mtnstopshiv.org.
21-December-2011
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