Microbicide PRO 2000: higher dose abandoned, lower dose studies continue

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Testing of a higher dose of the microbicide PRO 2000 is to be halted following a review by the Data Monitoring Committee of the UK Medical Research Council-sponsored trial.

PRO 2000 is an agent that prevents entry and attachment of HIV and others sexually transmitted infections to cells in the vaginal mucosa. It is being tested in a gel formulation that can be administered by women before sexual intercourse, in order to prevent HIV infection.

The interim analysis found that it was statistically unlikely that the high dose arm, in which women received a microbicide gel containing 2% PRO 2000, would show a significant protective effect against HIV infection compared to placebo in a large phase III trial being conducted among women in South Africa, Tanzania, Uganda and Zambia.

Glossary

microbicide

A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

formulation

The physical form in which a drug is manufactured or administered. Examples of formulations include tablets, capsules, powders, and oral and injectable solutions. A drug may be available in multiple formulations.

mucosa

Moist layer of tissue lining the body’s openings, including the genital/urinary and anal tracts, the gut and the respiratory tract.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

However the lower dose arm of the study, in which women receive a 0.5% dose of PRO 2000, will continue, and is expected to report results in 2009.

PRO 2000 is being developed as a microbicide by the Microbicide Development Programme, an international partnership of researchers, with funding from the UK’s Medical Research Council and the UK government’s Department for International Development. PRO 2000 is manufactured by Indevus Pharmaceuticals.

PRO 2000 is also being tested in a US National Institutes of Health randomised study, HPTN 035, which is comparing the lower 0.5% PRO 2000 dose with another microbicide product, BufferGel, and placebo. The study has recruited 3,100 women in South Africa, Malawi, Zimbabwe, Zambia, and the United States. HPTN 035 has been reviewed by its data monitoring committee on several occasions, no concerns have arisen, and the study is expected to report results in the summer of 2008.

Two other major microbicide studies were halted altogether in 2007 after it was discovered that women who received the active product, UsherCell, or cellulose sulphate, were more likely to become infected in one study.

A major international conference on microbicides takes place in Delhi, India from February 24-27th.