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 vicriviroc?
Vicriviroc is an investigational drug that is being studied for the treatment of HIV infection.
Vicriviroc belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
Vicriviroc works by attaching to one of two proteins on the surface of the immune cells. These proteins are called the CCR5 and CXCR4 co-receptors. Vicriviroc attaches to the CCR5 co-receptor. When vicriviroc attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.4
Vicriviroc requires boosting with the FDA-approved HIV medicine ritonavir (brand name: Norvir). (Boosting involves the use of a second drug to increase the effectiveness of the main [first] drug.)5
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.6
- 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.6
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the 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.6
In what phase of testing is vicriviroc?
Vicriviroc has been studied in Phase III clinical trials.2
The clinical development of vicriviroc for the treatment of HIV infection was discontinued in July 2010.3
What have recent studies shown about vicriviroc?
In two Phase III studies (known as the VICTOR-E3 and VICTOR-E4 studies), vicriviroc taken once daily was compared with placebo (a placebo is an inactive drug that is identical in appearance to the active drug being studied) in HIV-infected adults with R5-tropic HIV (virus that uses CCR5 as a co-receptor). The participants had taken HIV medicines previously (treatment-experienced). All study participants also received an optimized background regimen containing at least two fully active drugs. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.)7,8
In a combined analysis of VICTOR-E3 and VICTOR-E4, vicriviroc plus optimized background therapy did not work any better than placebo plus optimized background therapy. The majority of study participants were receiving at least three active drugs as part of their optimized background regimens. In an analysis of study participants receiving two or fewer active drugs in their background regimens, vicriviroc proved to be more effective than placebo. In terms of safety, vicriviroc was comparable to placebo.7,8
In a Phase II study, vicriviroc taken once daily was compared with the FDA-approved combination drug emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada) in adults infected with R5-tropic HIV. The participants had never taken HIV medicines before entering the study (treatment-naive). All study participants also received a background regimen containing the FDA-approved protease inhibitors atazanavir (brand name: Reyataz) and ritonavir (brand name: Norvir).9 (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)
In this study, the vicriviroc regimen had similar anti-HIV activity as the Truvada regimen. Anti-HIV activity was measured as a drop in viral load (amount of HIV in the blood) from the time of study entry to Week 48. However, in terms of efficacy, vicriviroc did not appear to work as well as Truvada. Efficacy was measured as the proportion of participants in each treatment group that had a viral load fewer than 50 copies/mL at Week 48. In terms of safety, more participants in the vicriviroc group discontinued the study because of side effects than in the Truvada group.9
What side effects might vicriviroc cause?
In the Phase III studies discussed under the previous question, side effects were similar in both the vicriviroc and placebo groups. The vicriviroc group had a greater percentage of participants stopping the study because of side effects than the placebo group did.7,8
In the Phase II study discussed under the previous question, no common adverse events were seen in the vicriviroc group. More vicriviroc than Truvada participants discontinued the study because of side effects.9
Information on possible side effects of the drug is not complete. If testing of vicriviroc continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying vicriviroc?
More information about vicriviroc-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 vicriviroc. 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.6
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 November 13, 2013.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on November 13, 2013.
3. Dunkle LM. Merck Research Laboratories. Vicriviroc Discontinued Investigator Letter. National AIDS Treatment Advocacy Project (NATAP): News Updates; 2010. Last accessed on November 13, 2013.
4. Strizki JM, Tremblay C, Xu S, et al. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-19. Last accessed on November 13, 2013.
5. Brown KC, Paul S, Kashuba AD. Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. Last accessed on November 13, 2013.
6. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on November 13, 2013.
7. Mascolini M. Vicriviroc Does Not Outdo Placebo Regimen in Phase 3 Trials. Conference Reports for National AIDS Treatment Advocacy Project (NATAP): 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Last accessed on November 13, 2013.
8. Caseiro MM, Nelson M, Diaz RS, et al. Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials. J Infect. 2012 Oct;65(4):326-35. Last accessed on November 13, 2013.
9. Dunkle LM, Gathe J, Zhou H, McCarthy M. Antiviral Effect of Vicriviroc (VCV) plus Ritonavir-Boosted Atazanavir (ATV/r) Similar to Tenofovir/emtricitabine (TEM) + ATV/r but Efficacy (%<50c/mL) Inferior as Initial Therapy. Abstract presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2010; Boston, MA. Abstract H-938a. Last accessed on November 13, 2013.
Last Reviewed: November 13, 2013
Last Updated: November 13, 2013