What is an investigational drug?
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.
What is SPL-7013?
SPL-7013 (brand name: VivaGel) is an investigational drug that is being studied to prevent sexual transmission of HIV and herpes simplex virus type 2 (HSV-2).5 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 sexually transmitted infections, such as HIV infection.6,7
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.6,7PrEP 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:
- inactivate HIV or other pathogens (also called disease-causing microorganisms);
- strengthen the body’s normal defenses;
- block HIV from attaching to healthy cells susceptible to infection;
- prevent HIV infection from spreading to other cells that are healthy.6
SPL-7013 works by blocking HIV from attaching to susceptible, healthy cells. SPL-7013 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
SPL-7013 is currently developed as a gel for vaginal use.5 SPL-7013 gel has also been studied for treating bacterial vaginosis and preventing recurrent bacterial vaginosis. (Bacterial vaginosis is an infection that causes unwanted overgrowth of certain bacteria in the vagina.)13
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.14
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.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
In what phase of testing is SPL-7013?
SPL-7013 gel for preventing transmission of HIV and HSV-2 is currently being studied in Phase I/II clinical trials.2
What have recent studies shown about SPL-7013?
A Phase I study known as SPL7013-006/MTN-004 investigated the safety and acceptability of SPL-7013 vaginal gel applied twice daily over 14 days in HIV-uninfected women. (In this study, acceptability referred to overall product like or dislike and the likelihood of future gel use.) SPL-7013 gel was compared to two different types of placebo gels. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) One of the placebo gels included the same base ingredients as in the SPL-7013 gel but didn’t include SPL-7013, which is the active ingredient. The other placebo gel also contained only inactive ingredients, including a gel thickener called hydroxycellulose (HEC).15
In the SPL7013-006/MTN-004 study, less than half of the women using SPL-7013 gel reported liking the product overall, and a little over half reported that they would likely use SPL-7013 gel in the future. In terms of safety, more participants in the SPL-7013 gel group had a genitourinary side effect than in the HEC gel placebo group. (Genitourinary side effects affect parts of the body that have a role in reproduction and/or removing waste products in the form of urine.) Changes in the normal balance of vaginal bacteria were seen in both the SPL-7013 and SPL-7013 placebo groups, but increases in bacterial vaginosis infections did not occur in either group.15
In another Phase I study known as SPL7013-004, the safety of twice-daily SPL-7013 gel was compared with a placebo gel. The gels were used over 14 days in HIV-uninfected women. In this study, mild genitourinary side effects and irritation to the tissue lining the vagina were more common in women using SPL-7013 than in women using placebo.16 In addition, participants using SPL-7013 gel had increases in certain immune cells or proteins that are associated with damage to the tissue lining the vagina.17
A Phase I/II study looked at the antiviral activity of single doses of SPL-7013 gel used on five separate occasions in 11 HIV-uninfected women. Using a SoftCup fitted in the vagina, study participants collected cervicovaginal fluid (CVF) samples before using the SPL-7013 gel, and then again immediately after or 1, 3, 12, or 24 hours after applying the gel. Upon exposing the samples of vaginal fluids to HIV-1 or HSV-2 in a laboratory, study researchers tested whether SPL-7013 could block HIV-1 and HSV-2 replication. In this study, SPL-7013 gel in human vaginal fluid samples demonstrated antiviral activity against HIV-1 and HSV-2. Antiviral activity was seen in the samples that were taken immediately after and up to 3 hours after the gel was applied. In terms of safety, some women experienced mild genitourinary side effects that may have been related to SPL-7013 gel.5
What side effects might SPL-7013 cause?
In the three studies discussed under the previous question, mild genitourinary side effects associated with SPL-7013 gel use were common.5,15,16 The most common genitourinary side effects in the SPL7013-006/MTN-004 study were difficult or painful sexual intercourse, bleeding or spotting between menstrual periods, and genital/vaginal burning or itching.15 Other side effects that have been associated with SPL-7013 gel use include mild damage to the vaginal/cervical tissue lining, bacterial vaginosis, and vaginal yeast infection.5,17
Because SPL-7013 is still being studied, information on possible side effects of the drug is not complete. As testing of SPL-7013 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying SPL-7013?
More information about SPL-7013-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.
I am interested in participating in a clinical trial of SPL-7013. How can I find more information about participating in a clinical trial?
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.
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2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on February 2, 2014.
3. Sonza S, Johnson A, Tyssen D, et al. Enhancement of Human Immunodeficiency Virus Type 1 Replication is Not Intrinsic to All Polyanion-Based Microbicides. Antimicrob Agents Chemother. 2009 Aug;53(8):3565-8. Last accessed on February 2, 2014.
4. American Medical Association website. Statement on a Nonproprietary Name Adopted by the USAN Council: Astodrimer. Last accessed on February 2, 2014.
5. 12. Price CF, Tyssen D, Sonza S, et al. SPL7013 Gel (VivaGel®) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans. PLoS One. 2011;6(9):e24095. Last accessed on February 2, 2014.
6. National Institute of Allergy and Infectious Diseases (NIAID). Topical Microbicides. Last accessed on February 2, 2014.
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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;5(8):e157; discussion e157. Last accessed on February 2, 2014.
9. International Partnership for Microbicides (IPM) website. Glossary: Polyanion. Last accessed on February 2, 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 February 2, 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 February 2, 2014.
12. Rupp R, Rosenthal SL, Stanberry LR. VivaGel™ (SPL7013 Gel): A candidate dendrimer--microbicide for the prevention of HIV and HSV infection. Int J Nanomedicine. 2007 December;2(4):561-6. Last accessed on February 2, 2014.
13. Starpharma: News, dated November 28, 2012. VivaGel phase 3 study results. Last accessed on February 2, 2014.
14. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on February 2, 2014.
15. McGowan I, Gomez K, Bruder K, et al. Phase 1 Randomized Trial of the Vaginal Safety and Acceptability of SPL7013 Gel (VivaGel®) in Sexually Active Young Women (MTN-004). AIDS. 2011 May 15;25(8):1057-64. Last accessed on February 2, 2014.
16. Cohen CR, Brown J, Moscicki AB, et al. A Phase I Randomized Placebo Controlled Trial of the Safety of 3% SPL7013 Gel (VivaGel®) in Healthy Young Women Administered Twice Daily for 14 Days. PLoS One. 2011 Jan 20;6(1):e16258. Last accessed on February 2, 2014.
17. Moscicki AB, Kaul R, Ma Y, et al. Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% SPL LTD 7013 gel (VivaGel®) to assess expanded safety. J Acquir Immune Defic Syndr. 2012 Feb 1;59(2):134-40. Last accessed on February 2, 2014.
Last Reviewed: February 2, 2014
Last Updated: February 2, 2014