The Ring Study to assess IPM’s monthly ARV ring for women
The International Partnership for Microbicides (IPM) today announced that a clinical trial called The Ring Study has been launched in Africa to determine whether a monthly vaginal ring containing the antiretroviral (ARV) drug dapivirine helps prevent HIV infection in women and is safe for long-term use. The Ring Study is the first Phase III efficacy trial of a microbicide ring for HIV prevention and will enroll a total of 1,650 women. The study is enrolling participants at four sites in South Africa and is expected to start at additional sites in Rwanda and Malawi in the coming months, pending regulatory and ethics approvals.
The dapivirine ring, developed by IPM, adapts a medical technology commonly used to deliver hormones to women – the vaginal ring – to the fight against HIV infection. The novel product could help address a critical gap in current HIV prevention strategies: the need for discreet female-initiated tools to prevent infection. The ring uses an innovative delivery method that slowly releases the ARV dapivirine over the course of one month to provide long-acting and easy-to-use protection against HIV. Dapivirine belongs to a class of ARVs known as non-nucleoside reverse transcriptase inhibitors, or NNRTIs, which have long been used to successfully treat HIV-1 and prevent mother-to-child transmission.
The Ring Study is part of a broader licensure program being conducted in partnership with the National Institutes of Health-funded Microbicide Trials Network (MTN). The full ring licensure program also includes MTN’s Phase III ASPIRE study (MTN-020), expected to launch in the coming months. Together, these sister studies are designed to evaluate the ring’s ability to prevent new HIV infections in women as well as its long-term safety.
“ARVs like dapivirine offer enormous promise for HIV prevention. Because the ring only needs to be replaced once a month, it has the potential to encourage consistent use and provide long-acting protection,” said Dr. Zeda Rosenberg, Chief Executive Officer at IPM. “Through this novel collaboration with MTN, Janssen, and multiple donors and clinical research centers, we aim to give women at risk of infection the ability to protect themselves in the most convenient and effective way possible.”
The Ring Study, also known as IPM 027, will enroll women ages 18 to 45 in two study arms. Approximately 1,100 women will be randomly assigned to use rings containing dapivirine, while 550 women will be assigned to the placebo group, which will use the same vaginal ring but without the active drug. Neither the women nor the study staff will know which product is being used by individual participants. In addition, MTN’s ASPIRE study will enroll 3,476 women at its trial sites in Malawi, South Africa, Uganda, Zambia and Zimbabwe, pending in-country regulatory and ethics approvals.
Women who participate in these studies receive ongoing and thorough testing and counseling to reduce their risk of acquiring HIV and other STIs, and are provided with condoms at each visit to the research center.
A number of recent studies have demonstrated that ARVs can be effective at preventing HIV, especially when used consistently. Because the ring is designed to deliver an ARV continuously over one month, it has the potential to address the challenge of adherence and help ensure effectiveness.
“Sustained delivery of antiretrovirals in a vaginal ring could be a game-changer for prevention of HIV in women,” said Dr. Sharon Hillier, principal investigator of MTN. “The Microbicide Trials Network’s partnership with IPM on effectiveness studies of this new technology will provide the most rapid and efficient pathway to licensure of this HIV prevention product.”
The entire ring licensure program will involve thousands of women and last approximately three years (2012-2015). In addition to IPM’s Ring Study and MTN’s ASPIRE study, the licensure program also includes planned studies to examine the ring’s safety in adolescents and peri- and postmenopausal women, condom compatibility and drug-drug interactions. Should the results from the package of studies show the dapivirine ring to be safe and effective, IPM will seek regulatory approval for product licensure and collaborate with key partners to help ensure the ring is made available at low cost to women in developing countries as soon as possible.
Globally, HIV/AIDS is one of the greatest threats to women’s health. It is the leading cause of death in women ages 15 to 44 worldwide. In sub-Saharan Africa, where the majority of new cases occur, 60 percent of people living with HIV are women, and young women ages 15 to 24 are more than twice as likely as young men to be infected with HIV.
Current HIV prevention options have not done enough to stop the spread of HIV among women. Existing methods may be unrealistic for women who are unable to negotiate with their male partners to use condoms and remain faithful, or for those who are married, want to have children or are at risk of violence. Microbicides like the dapivirine ring could empower women with a long-acting, discreet tool to protect themselves from infection and help bring us closer to a world without AIDS.
“We are very excited that this program is now underway and that the ring has the potential to be groundbreaking for women in Africa,” says Dr. Annalene Nel, Chief Medical Officer at IPM. “This product could expand the menu of HIV prevention options and give women a very practical way to protect their own health.”
The Ring Study has received all necessary approvals from the South African regulatory agency and ethics committees, with additional approvals in Malawi and Rwanda pending. The study is also in compliance with international clinical trial guidelines, and an independent Data Safety Monitoring Board (DSMB) will conduct regular reviews of this study to ensure the safety of participants at all times.
IPM is developing dapivirine for use as a microbicide through a royalty-free licensing agreement with Janssen R&D Ireland (previously Tibotec Pharmaceuticals), one of the Janssen pharmaceutical companies of Johnson & Johnson.
IPM is also developing multipurpose technologies, including a 60-day dapivirine-contraceptive ring under a grant from USAID, and maintains a diverse pipeline of microbicides. Other products in IPM’s pipeline include gels and films as well as other long-acting rings that could combine two or more ARVs to target HIV at different points in its life cycle and potentially maximize the overall protective effect.
The Ring Study and IPM’s work has been supported by a variety of past and present donors, including governments, foundations and multilateral organizations: Belgium, Canada, Denmark, France, Germany, Ireland, Netherlands, Norway, Spain, Sweden, the United Kingdom, the United States, the European Commission, the World Bank, UNFPA, the Bill & Melinda Gates Foundation, the Rockefeller Foundation, the OPEC Fund for International Development and the MAC AIDS Fund.