New microbicide for HIV prevention now in trials
Researchers have launched a clinical safety trial of VivaGel (SPL7013), a topical vaginal microbicide, for potential use in preventing the sexual transmission of HIV. The trial is being conducted in two sites, the University of South Florida in Tampa and the University of Puerto Rico in San Juan and it is supported by funding from the Division of AIDS at the National Institute of Allergy and Infectious Diseases and the National Institute of Child Health and Human Development.
Starpharma Pty. Ltd., of Melbourne, Australia, is looking at VivaGel as a candidate microbicide for the prevention of HIV/AIDS and genital herpes. The gel's active ingredient belongs to a class of compounds known as dendrimers, large molecular structures that incorporate multiple units of an active component on their surfaces. Each dendrimer in VivaGel incorporates 32 copies of the active component. Researchers believe the gel's unique molecular structure may hamper the ability of HIV to attach to and infect healthy cells.
Starpharma recently announced trial results that showed VivaGel was well tolerated and safe for continued development following topical penile application in men, says Jackie Farley, MBA, the company's chief executive officer. Acceptability was a secondary endpoint in this study, and interviews indicated that VivaGel would be acceptable to participants if shown to be protective against sexually transmitted infections, she notes.1 Findings from an earlier unpublished Phase I study of VivaGel in sexually abstinent women ages 18-43 indicate no safety concerns. Women were randomly assigned to receive different doses of the gel and closely examined during a seven-day inpatient stay in a clinical research unit.
Two sites eye drug
Screening of potential candidates for the trial began in July 2007. The trial, which will include 40 women, ages 18 to 24, who are sexually active and HIV-negative, is designed as a randomized placebo-controlled Phase I safety and acceptability trial with two treatment arms. Participants will be randomly assigned to one of two study groups, with one group applying VivaGel twice a day for two weeks, with participants in the other group using a placebo gel. All women in the study will be given condoms for use during each sexual interaction. Participation in the study is scheduled for three weeks, which will include the two-week period that gels are used.
If trial results prove satisfactory in terms of the safety profile and the acceptability, then the next step likely will be an extended safety study, where the study group may include a larger group of women who will use the product for a longer period of time, typically six months, says Ian McGowan, MD, PhD, visiting professor of medicine at the University of Pittsburgh School of Medicine and Magee-Womens Research Institute. McGowan is co-principal investigator of the Microbicide Trials Network and protocol chair for the current study of VivaGel.
The VivaGel study is the first of three trials expected to be launched this year by the Microbicide Trials Network (MTN). MTN is an HIV/AIDS clinical trials network established in 2006 by the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health.
The active ingredient in VivaGel, SPL7013, is a fourth-generation polylysine dendrimer. Thirty-two naphthalene disulfonate moieties, attached by amide linkages, are found on the molecule's surface. The structure prevents HIV infections by binding to the gp120 glycoprotein receptors on the virus's surface, an interaction which in turn stops HIV from attaching to receptors on T cells in the body.2 Given VivaGel's potential for infection prevention, Starpharma is looking at use of the product as a coating for condoms.
"The potential for VivaGel to be used as a condom coating reflects some of the growing momentum building to bring an effective preventative measure for HIV and STIs to market," notes Farley. "Starpharma has already signed an agreement with a leading manufacturer of condoms, which will include a program of evaluation and development and also commercialization rights covering condoms with VivaGel costing within a specific geographical region."
Preclinical animal studies on VivaGel have provided early evidence that VivaGel may serve as an effective contraceptive, says Farley. Further studies on the contraceptive ability of VivaGel are already under way, she notes.
- Paull J, Chen M, Millwood I, et al. SPL7013 Gel (VivaGel™), a topical microbicide in development for prevention of HIV and genital herpes, shown to be well tolerated and comparable with placebo after seven days administration in healthy males. Presented at the Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia; July 2007.
- Halford B. Dendrimers branch out. Chemical & Engineering News 2005; 83:30-36.