Africa, India test sites for anti-HIV microbicide

Cellulose sulfate tested in high-risk women

Phase III effectiveness clinical trials have begun for the potential anti-HIV microbicide cellulose sulfate (Ushercell), formerly called C31G, which already has demonstrated safety when used by women.1-4

If the trials go well, the product could be ready for approval by the Food and Drug Administration (FDA) by 2010.

Cellulose sulfate is being evaluated in two studies, each enrolling 2,400 women considered at high-risk of HIV infection, explains Henry L. Gabelnick, PhD, director of the Contraceptive Research and Development Programme (CONRAD) in Arlington, VA.

"In our studies, we’re looking at women who are at high risk from having multiple sex partners per week and multiple acts of intercourse," he says.

Preliminary data show the microbicide is as effective as a spermicide as anything else that’s available, and it’s worked quite well in vitro as an anti-HIV microbicide, Gabelnick says.

"We’re comfortable enough with everything we’ve seen in the spectrum of studies we’ve done to invest close to $25 million to do this study," he adds.

CONRAD is conducting the clinical trials for Polydex of Toronto, Canada, with whom the organization has worked for a number of years, Gabelnick continues.

"We have in place agreements guaranteeing public-sector pricing, preferential pricing for governments and multinational organizations, etc., who would be purchasing this product for those who are disadvantaged," he says.

The success of the product depends in part on how well it works as a contraceptive, Gabelnick adds.

"If a good contraceptive product comes along that’s also microbicidal, there will be a market for it in developed countries," he points out, adding that nonoxynol-9 continues to stay on the market as a contraceptive, despite the widespread media attention paid to its failure as an anti-HIV microbicide. "The fact that cellulose sulfate is a large molecule convinces us it won’t get absorbed, and it won’t cause any side effects," Gabelnick says. "There were no adverse events, no problems so far, and in the earlier studies, we actually had it evaluated for use up to four times a day for two weeks."

One of the Phase III studies is conducted in Nigeria, and the other study, which is expected to be under way at six sites this spring will be held in West Africa, Uganda, South Africa, and two sites in India or another Southeast Asia location, he says.

Cellulose sulfate is intended to work as both a contraceptive and a microbicide that blocks infection by HIV and other sexually transmitted diseases (STDs), Gabelnick notes.

"It adheres to the virus and blocks its entry into the cell," he says. "It’s got a fairly broad spectrum, with activity — at least in vitro and in some animal models — against chlamydia."

However, it’s designed primarily to block HIV entry, Gabelnick says.

The microbicide also is being tested in the United States in a study that is designed to study its effectiveness as a contraceptive, he notes.

It’s being studied in a 6% solution that forms a mildly high viscosity gel that is pre-applicated to make certain the dose is consistent, Gabelnick explains.

"Ultimately, it could be in a reusable dispenser or tube, and we’ll look at alternative formulations like foaming tablets that are placed in the vagina," he says.

Foaming tablets are placed in the vagina where a mild reaction takes place and causes the tablet to foam and spread in that manner, Gabelnick explains.

An earlier study noted that C31G is at least as safe and acceptable for male penile exposure as 3% nonoxynol-9.5

Cellulose sulfate as a microbicide would be of interest to women who already use lubricants of some kind, and so it would not be noticeable to their partners; or to women who could tell their partners that they are using a contraceptive and/or microbicide, Gabelnick says.

If the couple were accustomed to having dry sex, then the product would be noticeable, he adds.

"My personal belief is that what we’re trying to do is give women the ability to take the initiative, but not necessarily to use the product surreptitiously," Gabelnick says. "We’re trying to use something as discreet as possible, and in acceptability studies done so far, we’ve gotten feedback that it’s acceptable to both women and their partners."

For populations in which women would not be able to use a microbicide that also works as a contraceptive, there might be other options as Carraguard and other products are moving through the microbicide pipeline ahead of cellulose sulfate, Gabelnick says.

On the other hand, women who need a product to prevent pregnancy would be at an advantage with cellulose sulfate because it also could protect them against STDs, he adds.

"If a woman does want her partner’s agreement to use the product, it’s a lot easier to sell it to a man that she’s using this to regulate fertility than it is to say she’s using it because she thinks he’s been sleeping around," Gabelnick says.

CONRAD has signed an agreement for collaborative research on microbicide development with the Indian Council of Medical Research to work together in a joint program for conducting clinical trials and screening new drugs, he points out.

"Right now most of our emphasis is on clinical trials of this microbicide," Gabelnick adds.

References

1. D’Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des 2004; 10:315-336.

2. Bax R, Douville K, McCormick D, et al. Microbicides — Evaluating multiple formulations of C31G. Contraception 2002; 66:365-368.

3. Mauck CK, Weiner DH, Creinin MD, et al. A randomized Phase I vaginal safety study of three concentrations of C31G vs. Extra Strength Gynoll II. Contraception 2004; 70:233-240.

4. Ballagh SA, Baker JM, Henry DM, et al. Safety of single daily use for one week of C31G HEC gel in women. Contraception 2002; 66:369-375.

5. Mauck CK, Frezieres RG, Walsh TL, et al. Male tolerance study of 1% C31G. Contraception 2004; 70:221-225.