MTN-008 Expanded Safety Study of Tenofovir Gel in Pregnant and Breastfeeding Women
Study Overview
MTN-008 is a Phase I study that aims to find out whether using a vaginal microbicide called tenofovir gel daily for one week is safe for women late in pregnancy and while breastfeeding. Tenofovir is an antiretroviral (ARV) drug that is commonly used in tablet form to treat people with HIV in combination with other ARVs. The gel form of tenofovir holds great promise for preventing HIV among women, and researchers are hopeful it will be the first HIV prevention product approved for widespread use. MTN-008 is part of a comprehensive research program designed to take incremental steps toward determining whether tenofovir gel can safely and effectively protect women against HIV during all stages of pregnancy and motherhood.
The study is a follow-up to MTN-002, which found that a single dose of tenofovir gel given to pregnant women hours before scheduled Cesarean delivery was safe and well-tolerated by both mother and infant. Based on these reassuring findings, the researchers conducting MTN-008 are increasing dosing frequency to daily use for one week during at-term and close-to-term pregnancy. They plan to evaluate the safety of the drug and assess how much active drug is absorbed during pregnancy and subsequently transferred to the fetus. In breastfeeding mothers, the researchers will measure drug levels in breast milk and assess whether the drug is transferred to the baby.
MTN-008 is being conducted at Magee-Womens Hospital of the University of Pittsburgh Medical Center and the University of Alabama, Birmingham (UAB), through 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 (NIAID) with co-funding from the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), all components of the U.S. National Institutes of Health. Richard Beigi, M.D., M.Sc., of the University of Pittsburgh School of Medicine and Magee-Womens Hospital of the University of Pittsburgh Medical Center, is leading the study.
Why this Study is Important
Nearly 16 million women around the world are living with HIV, which represents close to half of all people who are infected. Most of these women acquired HIV from unprotected vaginal sex. Microbicides are products designed to prevent or reduce the risk of HIV or other sexually transmitted infections when used in the vagina or rectum, and are being developed primarily for use by sexually active women. Yet, there is very little information about whether these products can be safely used by pregnant and breastfeeding women, most of whom remain sexually active and continue to be at risk for HIV. In fact, some studies suggest that women may be particularly susceptible to HIV during pregnancy due to heightened immune responses or hormonal changes that affect the mucosal lining in the vagina. Because women often continue to use medications during pregnancy, knowing whether microbicides are safe to use in this population before they become readily available also is vitally important.
Tenofovir gel is the first and only vaginal microbicide that has been shown in a large clinical trial to reduce the risk of HIV. Results of this study, called CAPRISA 004, found 39 percent fewer infections among HIV-negative women who used tenofovir gel before and after sex compared to women who used a placebo gel. The MTN is conducting a major large-scale trial called VOICE –Vaginal and Oral Interventions to Control the Epidemic – that is testing whether daily use of tenofovir gel, or daily use of an ARV tablet, can reduce women’s risk for HIV among 5,000 women in southern Africa. The U.S. Food and Drug Administration (FDA) has indicated it will consider approving tenofovir gel as an HIV prevention method for women based primarily on its review of the results of CAPRISA 004 and VOICE, which are expected in 2013. MTN-008 will provide critical information about the safety of tenofovir gel during pregnancy and lactation, which the FDA also considers essential to its decision whether to approve the gel.
How the Study is Being Conducted
MTN-008 is a Phase I expanded safety study looking at daily use of tenofovir gel for one week by pregnant women in the third trimester of pregnancy, and the daily use of the gel for one week by breastfeeding mothers four to 26 weeks after they have given birth. The study will include approximately 105 HIV-negative mother-infant pairs (90 pairs in the pregnancy group and 15 pairs in the nursing group). The tests and procedures performed as part of the study include urine and blood tests, vaginal and cervical fluid collection, and pelvic and physical examinations to determine how the drug is absorbed and distributed in the body. Once a woman gives birth, researchers also will measure the presence of the gel’s active ingredient in the umbilical cord blood. For the group of breastfeeding women, the presence of active drug will be measured in breast milk and in blood samples from both mother and infant.
The Product Being Studied
MTN-008 is evaluating tenofovir formulated as a vaginal gel. Tenofovir belongs to a class of ARVs called nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which act against HIV by targeting a key enzyme the virus needs to copy in order to take over a host cell. Each dose of tenofovir gel contains approximately 40 mg of active drug. Both the tablet and gel forms of tenofovir were developed by Gilead Sciences, Inc., of Foster City, Calif., U.S., which assigned rights for the topical gel to CONRAD, of Arlington, Va., and the International Partnership for Microbicides of Silver Spring, Md., in December 2006.
Participant Safety
MTN-008 was designed according to the most rigorous international medical practice and ethical standards and includes numerous measures to protect the safety and well-being of participants. As with all MTN studies, MTN-008 incorporates a multi-tiered safety review process. This process includes clinicians evaluating participants at the trial sites; a team at the statistical and data management center (SDMC) that assesses incoming reports on a daily basis; three MTN physicians – two specializing in infectious diseases and HIV and the other in obstetrics and gynecology – who review summary reports and any concerns raised by site clinicians or the SDMC; monthly reviews by a protocol safety review team; and periodic review by a study monitoring committee. MTN-008 was reviewed by the Institutional Review Boards (IRBs) at the University of Pittsburgh and UAB, to ensure that it is scientifically valid and ethically conducted. Written informed consent will be obtained from all participants prior to enrollment to ensure they understand the procedures, as well as possible risks and benefits of the study.
Funding
MTN-008 is being funded by NIAID and NICHD. CONRAD is providing tenofovir gel and the gel applicators for MTN-008.
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More information about MTN-008 and other MTN studies can be found at http://www.mtnstopshiv.org/news.
About the Microbicide Trials Network
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 preventing or reducing the sexual transmission of HIV through the development and evaluation of products applied topically to mucosal surfaces or administered orally.
20-June-2011
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20-Jun-2011
