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 astodrimer?
Astodrimer (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).3 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.4,5
Astodrimer belongs to a group of drugs called polyanion-based entry inhibitors.6 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.7-9
Astodrimer is currently developed as a gel for vaginal use.3 Astodrimer gel has also been studied for treating bacterial vaginosis and is currently being studied for preventing recurrent bacterial vaginosis. (Bacterial vaginosis is an infection that causes unwanted overgrowth of certain bacteria in the vagina.)10-12
How do topical microbicides work?
Topical microbicides can also be referred to as topical pre-exposure prophylaxis (PrEP) products.4,5 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).5,13 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.4
Astodrimer works by blocking HIV from attaching to susceptible, healthy cells.3,6
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 effective and must show continued safety 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 astodrimer?
Astodrimer gel for preventing transmission of HIV and HSV-2 has been studied in Phase I/II clinical trials.2
What are some studies on astodrimer?
Study Name: SPL7013-006 (MTN-004)
Location: United States
Participants: HIV-uninfected women
Purpose: To look at the safety and acceptability of astodrimer vaginal gel used over 14 days. (In this study, acceptability referred to overall product like or dislike and the likelihood of future gel use.)
Study Design: Astodrimer 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.) Participants applied the gels vaginally and twice daily. Participants were randomly assigned to one of the following three groups:
- Astodrimer gel
- Astodrimer placebo gel. (Astodrimer placebo gel contained the same base ingredients as in the astodrimer gel but didn’t include astodrimer, which is the active ingredient.)
- Hydroxycellulose (HEC) placebo gel. (HEC is a gel thickener.)
- Less than half of the women using astodrimer gel reported liking the product overall, and a little over half reported that they would likely use astodrimer gel in the future.
- In terms of safety, more participants in the astodrimer gel group had a genitourinary side effect than in the HEC placebo gel 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 astodrimer and astodrimer placebo groups, but increases in bacterial vaginosis infections did not occur in either group.15,16
Note: While SPL7013-006 was ongoing, researchers expanded the gel acceptability assessment in women participating in this study by simultaneously conducting a study known as ATN 062. ATN 062 gathered acceptability data by using questionnaires, teleconferences, and an interactive voice reporting system where women reported their experiences with using the study gels. Participants in ATN 062 reported problems with all three gels; the most common complaints were gel leakage, interference with sexual behavior, and decreased sexual satisfaction.17,18
Study Name: SPL7013-004
Location: United States and Kenya
Participants: HIV-uninfected women
Purpose: To look at the safety of astodrimer gel when it’s used twice a day.
Study Design: Participants used either astodrimer gel or placebo gel twice a day for 14 days.
- Mild genitourinary side effects and irritation to the tissue lining the vagina were more common in women using astodrimer than in women using placebo.
- Participants using astodrimer gel had increases in certain immune cells or proteins that are associated with damage to the tissue lining the vagina.19-21
Study Name: SPL7013-003
Participants: 11 HIV-uninfected women
Purpose: To look at the antiviral activity of single doses of astodrimer gel used on five separate occasions.
Study Design: Using a SoftCup fitted in the vagina, study participants collected cervicovaginal fluid (CVF) samples before using astodrimer gel, and then again immediately after applying the gel 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 astodrimer could block HIV-1 and HSV-2 replication.
- The astodrimer gel in the human vaginal fluid samples showed 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 astodrimer gel.3,22
What side effects might astodrimer cause?
In the three studies discussed under the previous question, mild genitourinary side effects associated with astodrimer gel use were common.3,15,20 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 astodrimer gel use include mild damage to the vaginal/cervical tissue lining, bacterial vaginosis, and vaginal yeast infection.3,21
Because astodrimer gel is still being studied, information on possible side effects of the drug product is not complete. As testing of astodrimer gel continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying astodrimer?
More information about astodrimer-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 astodrimer. 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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/1379746-42-5. Last accessed on April 8, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174146/. Last accessed on April 8, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). Topical Microbicides. Available at: http://www.niaid.nih.gov/topics/hivaids/research/prevention/pages/topicalmicrobicides.aspx. Last accessed on April 8, 2015.
- Shattock RJ, Rosenberg Z. Microbicides: Topical Prevention against HIV. Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281595/. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715623/. Last accessed on April 8, 2015.
- International Partnership for Microbicides (IPM) website. Glossary: Polyanion. Available at: http://www.ipmglobal.org/our-work/glossary/polyanion. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590048/. Last accessed on April 8, 2015.
- Garg AB, Nuttall J, Romano J. The future of HIV microbicides: challenges and opportunities. Antivir Chem Chemother. 2009;19(4):143-50. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=a04ed6be-7c85-4bc7-9f9d-b9f5e9290a52. Last accessed on April 8, 2015.
- Starpharma: Press Release, dated November 28, 2012. VivaGel phase 3 study results. Available at: http://www.starpharma.com/news/139. Last accessed on April 8, 2015.
- Starpharma Pty Ltd. A Phase 3, Double-blind, Multicentre, Randomised, Placebo-controlled Study to Determine the Efficacy and Safety of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 5, 2014. NLM Identifier: NCT02237950. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02237950. Last accessed on April 8, 2015.
- Starpharma Pty Ltd. A Phase 3, Double-blind, Multicentre, Randomised, Placebo-controlled Study to Determine the Efficacy and Safety of SPL7013 Gel to Prevent the Recurrence of Bacterial Vaginosis. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 5, 2014. NLM Identifier: NCT02236156. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02236156. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494562/. Last accessed on April 8, 2015.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103767/. Last accessed on April 8, 2015.
- Starpharma Pty Ltd. Phase 1 Study of the Safety and Acceptability of 3% w/w SPL7013 Gel (VivaGel™) Applied Vaginally in Sexually Active Young Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2007. NLM Identifier: NCT00442910. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00442910. Last accessed on April 8, 2015.
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Microbicide-Use Adherence, Acceptability, and Attitudes Among Sexually Active Young Women Participating in a Phase I Microbicide Trial (MTN 004) "Tell Juliana". In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 21, 2007. NLM Identifier: NCT00490152. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00490152. Last accessed on April 8, 2015.
- Carballo-Diéguez A, Giguere R, Dolezal C, et al. "Tell Juliana": Acceptability of the Candidate Microbicide VivaGel® and Two Placebo Gels among Ethnically Diverse, Sexually Active Young Women Participating in a Phase 1 Microbicide Study. AIDS Behav. 2012 Oct;16(7):1761-74. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272128/. Last accessed on April 8, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). An Expanded Phase I Randomized Placebo Controlled Trial of the Safety and Tolerability of 3 Percent w/w SPL7013 Gel (VivaGel™) in Healthy Young Women When Administered Twice Daily for 14 Days. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 25, 2006. NLM Identifier: NCT00331032. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00331032. Last accessed on April 8, 2015.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024437/. Last accessed on April 8, 2015.
- Moscicki AB, Kaul R, Ma Y, et al. Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% SPL 7013 gel (VivaGel®) to assess expanded safety. J Acquir Immune Defic Syndr. 2012 Feb 1;59(2):134-40. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261360/. Last accessed on April 8, 2015.
- Starpharma Pty Ltd. Assessment of Local Retention and Duration of Activity of SPL7013 Following Vaginal Application of 3% SPL7013 Gel (VivaGel) in Healthy Volunteers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 21, 2008. NLM Identifier: NCT00740584. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00740584. Last accessed on April 8, 2015.
Last Reviewed: April 8, 2015