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.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is vicriviroc?
Vicriviroc is an investigational drug that was first studied for the treatment of HIV infection. In 2010, the study of vicriviroc for HIV treatment was discontinued.3
Currently, vicriviroc-containing topical microbicides to prevent sexual transmission of HIV infection in women are being studied in early clinical trials.4,5 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
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 1 of 2 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.8
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.9
- 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.9
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.9
(Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.)
In what phase of testing is vicriviroc?
Vicriviroc for HIV treatment has been studied in Phase III clinical trials.2 The development of vicriviroc for the treatment of HIV infection was discontinued in July 2010.3
Vicriviroc-containing topical microbicides to prevent sexual transmission of HIV infection in women have been studied in Phase I clinical trials.4,5
What are some studies on vicriviroc?
Note: The study of oral vicriviroc for HIV treatment was discontinued in 2010. The company developing the drug announced that this decision was based on data from a Phase II trial in adults who had never taken HIV medicines before and 2 Phase III trials in adults who had previous experience with antiretroviral therapy. (Antiretroviral therapy, or ART, is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.) In these trials, vicriviroc failed to show that it was more effective than currently approved HIV medicines already in use.3,10,11
Study Names: P04875; NCT00551018
Sponsor: Merck Sharp & Dohme Corp.
Location: Not available
- Participants were HIV-infected adults who had never been on ART before entering the study, or had been on ART for 4 weeks or less (with exceptions). None of the participants had received ART for 8 weeks before entering the study.
- All participants were infected with R5-tropic HIV (virus that uses CCR5 as a co-receptor).
- Participants had viral load levels of 2,000 copies/mL or more. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 cell counts of 100 cells/mm3 or less. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
: The purpose of this study was to compare vicriviroc's safety and effectiveness to that of the FDA-approved combination drug emtricitabine
/tenofovir disoproxil fumarate
(brand name: Truvada
). The researchers evaluated the effects of the drugs after 48 weeks and 96 weeks of treatment.12
: (1) VICTOR-E3; P04405AM5; NCT00523211
and (2) VICTOR-E4; P04889AM8; NCT00474370
: Merck Sharp & Dohme Corp.
: North and South America, Europe, and South Africa
- Participants were HIV-infected people 16 years of age and older who had taken HIV medicines before entering the study.
- All participants were infected with R5-tropic HIV.
- Participants had viral loads greater than 1,000 copies/mL within 60 days of the start of the study.
- Before the study started, participants had been on ART that included 3 or more ARVs for at least 4 weeks and had had no changes to their ART, or they had received no ART for at least 4 weeks.
- Participants had drug resistance to at least 2 ARV drug classes (nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) or had taken at least 6 months of ART that included at least 2 of the following: 1 NRTI, 1 NNRTI, or 2 PIs (excluding a low dose of ritonavir, brand name: Norvir).
: VICTOR-E3 and VICTOR-E4 were identical studies designed to compare vicriviroc to placebo
in terms of safety and effectiveness. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)
For more details on the studies listed above, see the Health Professional version
Vicriviroc is being developed into microbicide
products to prevent sexually acquired HIV infection in women. Two Phase I studies looked at the safety and drug properties of intravaginal
rings (IVRs) containing vicriviroc.4,5
In a Phase I study (MTN-027; NCT02356302
), investigators evaluated (1) an IVR containing vicriviroc, (2) an IVR containing MK-2048 (an investigational integrase
inhibitor), and (3) a combination IVR containing both vicriviroc and MK-2048. (The combination IVR is also known as MK-2048A.) Each of the 3 IVRs were compared to a placebo IVR.4
Another Phase I study (MTN-028; NCT02419456
) looked at the combination IVR (MK-2048A) at 2 different dose strengths.5
What side effects might vicriviroc cause?
In the Phase III studies discussed under the previous question (NCT00523211 and NCT00474370), 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.13
In the Phase II study discussed under the previous question (NCT00551018), no common side effects were seen in the vicriviroc group. More vicriviroc than Truvada participants discontinued the study because of side effects.11
Clinical trials of intravaginal rings containing vicriviroc are just beginning. As testing of intravaginal rings containing vicriviroc continues, 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.
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.9
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/306296-47-9. Last accessed on December 21, 2016.
- 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 December 21, 2016.
- Dunkle LM. Merck Research Laboratories. Vicriviroc Discontinued Investigator Letter. National AIDS Treatment Advocacy Project (NATAP): News Updates; 2010. Available at: http://www.natap.org/2010/newsUpdates/071510_02.htm. Last accessed on December 21, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 2, 2015. NLM Identifier: NCT02356302. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02356302. Last accessed on December 21, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). Phase 1 Pharmacokinetic Trial of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 14, 2015. NLM Identifier: NCT02419456. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02419456. Last accessed on December 21, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID Research on Topical Microbicides. Available at: http://www.niaid.nih.gov/topics/hivaids/research/prevention/pages/topicalmicrobicides.aspx. Last accessed on December 21, 2016.
- 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 December 21, 2016.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315929/. Last accessed on December 21, 2016.
- 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 December 21, 2016.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22634184. Last accessed on December 21, 2016.
- 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. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d89fb4da-4268-4d6b-88ee-4f4ebcd548de&cKey=bb11cf2f-7e42-4aa1-bffa-d364f8cc3e6d&mKey=%7b93AEED6A-54D4-4EF6-99BD-A9B3CE9FACD9%7d. Last accessed on December 21, 2016.
- Merck Sharp & Dohme Corp. Efficacy and Safety of VICRIVIROC in HIV-Infected Treatment-Naïve Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 29, 2007. NLM Identifier: NCT00551018. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00551018. Last accessed on December 21, 2016.
- 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. Available at: http://www.natap.org/2010/CROI/croi_12.htm. Last accessed on December 21, 2016.
- Merck Sharp & Dohme Corp. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E3). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 30, 2007. NLM Identifier: NCT00523211. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00523211. Last accessed on December 21, 2016.
- Merck Sharp & Dohme Corp. Vicriviroc in Combination Treatment With an Optimized ART Regimen in HIV-Infected Treatment-Experienced Subjects (VICTOR-E4). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 15, 2007. NLM Identifier: NCT00474370. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00474370. Last accessed on December 21, 2016.
Last Reviewed: December 21, 2016