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.
Cenicriviroc is an investigational drug that is being studied for the treatment of HIV infection.
Cenicriviroc 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.
Cenicriviroc works by attaching to one of two proteins on the surface of the immune cells. These proteins are called the CCR5 and CXCR4 coreceptors. Cenicriviroc attaches to the CCR5 coreceptor. When cenicriviroc attaches to the CCR5 coreceptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.3
Cenicriviroc also appears to block another receptor known as CCR2. The CCR2 receptor is associated with inflammatory diseases. The potential benefits of blocking the CCR2 receptor in people with HIV are being studied.4,5
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 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.6
In a 48-week Phase IIb study (known as Study 202), two different strengths of cenicriviroc taken orally and once daily were compared to the HIV medicine efavirenz (an FDA-approved non-nucleoside reverse transcriptase inhibitor [NNRTI]; brand name: Sustiva). Participants were HIV-infected adults with R5-tropic HIV (virus that uses CCR5 as a coreceptor). Participants had never taken HIV medicines before entering the study (called treatment-naive).7,8
During the study, participants also received the FDA-approved medicine Truvada (a combination tablet that contains the HIV medicines emtricitabine [brand name: Emtriva] and tenofovir disoproxil fumarate [brand name: Viread]) as part of their background regimen. (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.) Also, depending on which treatment group participants were assigned to, they took placebos of some of the medicines. (A placebo is an inactive drug that is identical in appearance to the active drug.)7,8
In this study, cenicriviroc was as effective as efavirenz at reducing HIV viral load (the amount of HIV in a blood sample). Cenicriviroc also appeared to block the CCR2 receptor and decrease levels of a certain marker of inflammation called soluble CD14. (Soluble CD14 may be associated with an increased risk of death and other disease states in HIV-infected individuals.) In terms of safety, fewer cenicriviroc participants than efavirenz participants experienced a severe side effect or dropped out of the study because of a side effect.8-11
The company developing cenicriviroc is planning Phase III clinical trials to investigate a fixed-dose combination (FDC) tablet containing cenicriviroc plus the FDA-approved medicine lamivudine (brand name: Epivir).12
In addition, a Phase II study will be looking at the effectiveness and safety of cenicriviroc as a treatment for mild to moderate HIV-associated neurocognitive disorder (HAND).13 (HAND ranges from mild problems with memory, language, and reasoning to the more severe HIV-associated dementia [HAD].)
In Study 202 discussed under the previous question, side effects related to treatment occurred in participants across all study groups, but occurred in a smaller percentage of cenicriviroc-treated participants than efavirenz-treated participants. Total and LDL cholesterol levels decreased in participants receiving cenicriviroc, but increased in participants receiving efavirenz.8,9
Because cenicriviroc is still being studied, information on possible side effects of the drug is not complete. As testing of cenicriviroc continues, additional information on possible side effects will be gathered.
More information about cenicriviroc-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.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.
Last Reviewed: September 3, 2014