An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
PRO-2000 is an investigational drug that has been studied to prevent sexual transmission of HIV and other sexually transmitted infections (STIs). It is a type of drug product called a topical microbicide. Topical microbicides are products that are applied to the vagina or rectum (such as gels, films, or creams) or inserted into the vagina (such as vaginal rings) to prevent getting STIs, such as HIV infection.6
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.6,7 PrEP means using a medicine before possible exposure to a virus or bacteria to reduce the risk of becoming infected with the virus or bacteria. Topical microbicides to prevent HIV infection are designed to work close to where they are applied and near to where HIV might enter the body (through the vagina or rectum).7,8 They may prevent HIV transmission in a number of ways. For example, HIV topical microbicides might:
PRO-2000 works by blocking HIV from attaching to susceptible, healthy cells. PRO-2000 belongs to a group of drugs called polyanion-based entry inhibitors.3 Polyanion-based entry inhibitors interact through an electrostatic association with the surface of viruses such as HIV. The interaction between the negatively charged surface of a polyanion-based entry inhibitor and HIV’s positively charged surface may prevent HIV from attaching to, entering, or infecting healthy cells.9,10,11
PRO-2000 is currently in a gel form. The gel has been studied for vaginal use.12,13
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.14
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.14
PRO-2000 vaginal gel has been studied in Phase III clinical trials.2
PRO-2000 vaginal gel was found to be ineffective as a topical microbicide for preventing HIV infection in Phase II and III clinical studies.5
In a Phase II/IIb study known as HPTN 035, the safety and effectiveness of two different investigational microbicide gels—PRO-2000 gel and Carbopol 974P (brand name: BufferGel)—were compared to the safety and effectiveness of a placebo gel and to no gel. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Participants in this study were instructed to apply gels vaginally 1 hour or less before each episode of vaginal intercourse. Women used the gels for approximately 20 months.12
In the HPTN 035 study, PRO-2000 vaginal gel was found to be about 30% effective in protecting HIV-uninfected women from acquiring HIV. This result, however, was not statistically significant, meaning that the gel’s effect may have been the result of chance rather than a true protective effect. BufferGel, the other investigational microbicide tested in this study, had no effect on preventing HIV infection in women. In terms of safety, both PRO-2000 and BufferGel were determined to be safe.5,12
In a large Phase III study known as MDP 301, the safety and effectiveness of two different strengths of PRO-2000 vaginal gel were compared to the safety and effectiveness of a placebo gel in HIV-uninfected women. Study participants were instructed to apply gels vaginally within an hour before sexual intercourse. Women used the gels for approximately 52 weeks. In this study, neither strength of PRO-2000 gel was effective in reducing the risk of HIV infection or other STIs. In terms of safety, side effects were similar in the women using the PRO-2000 gel and in those using placebo gel.5,13
In both the Phase II/IIb and Phase III studies discussed under the previous question, PRO-2000 vaginal gel was determined to be safe.5,12,13 The side effect most commonly reported by women in the MDP 301 study was genital itching.13
Information on possible side effects of the drug is not complete. If testing of PRO-2000 vaginal gel continues, additional information on possible side effects will be gathered.
More information about PRO-2000-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.14
Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
1. United States National Library of Medicine. ChemIDplus Advanced. Last accessed on March 20, 2014.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on March 20, 2014.
3. Sachdev DD, Zerhouni-Layachi B, et al. The Differential Binding and Activity of PRO 2000 Against Diverse HIV-1 Envelopes. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):125-9. Last accessed on March 20, 2014.
4. Endo Pharmaceuticals Inc.: News Release, dated January 5, 2009. Endo Pharmaceuticals to Acquire Indevus Pharmaceuticals. Last accessed on March 20, 2014.
5. National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated December 14, 2009. NIAID Web Bulletin: Major Study Finds Anti-HIV Gel Ineffective Among Women. Last accessed on March 20, 2014.
6. National Institute of Allergy and Infectious Diseases (NIAID). Topical Microbicides. Last accessed on March 20, 2014.
7. Shattock RJ, Rosenberg Z. Microbicides: Topical Prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Last accessed on March 20, 2014.
8. Cranage M, Sharpe S, Herrera C, et al. Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-Exposure Application of Tenofovir Gel. PLoS Med. 2008 Aug ;5(8):e157. Last accessed on March 20, 2014.
9. International Partnership for Microbicides (IPM) website. Glossary: Polyanion. Last accessed on March 20, 2014.
10. Fletcher PS, Wallace GS, Mesquita PM, Shattock RJ. Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants. Retrovirology. 2006 Aug 1;3:46. Last accessed on March 20, 2014.
11. Garg AB, Nuttall J, Romano J. The future of HIV microbicides: challenges and opportunities. Antivir Chem Chemother. 2009;19(4):143-50. Last accessed on March 20, 2014.
12. Abdool Karim SS, Richardson BA, Ramjee G, et al. Safety and Effectiveness of BufferGel and 0.5% PRO2000 Gel for the Prevention of HIV Infection in Women. AIDS. 2011 Apr 24;25(7):957-66. Last accessed on March 20, 2014.
13. McCormack S, Ramjee G, Kamali A, et al. PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial. Lancet. 2010 Oct 16;376(9749):1329-37. Last accessed on March 20, 2014.
14. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on March 20, 2014.
Last Reviewed: March 20, 2014
Last Updated: March 20, 2014