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 cenicriviroc?
Cenicriviroc is an investigational drug that is being studied for the treatment of HIV infection and HIV-associated neurocognitive disorders (HAND). (HAND ranges from mild problems with memory, language, and reasoning to the more severe HIV-associated dementia [HAD].) Cenicriviroc is also being studied to treat 2 liver diseases called nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC).3-5
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 a protein on the surface of the immune cells. The protein is called the CCR5 co-receptor. When cenicriviroc attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.6
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.7,8
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
In what phase of testing is cenicriviroc?
Cenicriviroc has been studied in a Phase IIb clinical trial.2,3
What are some studies on cenicriviroc?
Study Name: TBR-652-2-202 (Study 202); NCT01338883
Sponsor: Tobira Therapeutics, Inc.
Location: United States and Puerto Rico
- Participants were HIV-infected adults who had never taken HIV medicines before (also called treatment-naive). All participants were infected with R5-tropic HIV (virus that uses CCR5 as a co-receptor).
- Participants had a viral load of at least 1,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 counts of at least 200 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell—in a sample of blood and is an important indicator of immune function.)
Purpose: The purpose of this study was to compare the safety and effectiveness of 2 different doses of cenicriviroc versus the HIV medicine efavirenz (an FDA-approved non-nucleoside reverse transcriptase inhibitor [NNRTI]; brand name: Sustiva).3,10
For more details on this study, see the Health Professional version.
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).11
In addition, a Phase II study (NCT02128828) will be looking at the effectiveness and safety of cenicriviroc as a treatment for mild to moderate HAND.4
What side effects might cenicriviroc cause?
In Study 202 (NCT01338883) discussed under the previous question, the most common side effects associated with cenicriviroc were nausea, headache, diarrhea, and abnormal dreams. One participant receiving cenicriviroc had a severe, symptomless elevation in a liver enzyme level, but it was temporary.3,10
In this study, 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 low-density lipoprotein (LDL) cholesterol levels decreased in participants receiving cenicriviroc, but increased in participants receiving efavirenz. (LDL cholesterol is one type of cholesterol.) More participants in the efavirenz group dropped out of the study because of side effects than in the cenicriviroc group.12,13
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.
Where can I get more information about clinical trials studying cenicriviroc?
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.
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/497223-25-3. Last accessed on October 13, 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 October 13, 2016.
- Tobira Therapeutics, Inc. A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR 652) or Once-Daily EFV, Each With Open-Label FTC/TDF, in HIV 1-Infected, Antiretroviral Treatment-Naïve, Adult Patients With Only CCR5-Tropic Virus. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 18, 2011. NLM Identifier: NCT01338883. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01338883. Last accessed on October 13, 2016.
- University of Hawaii. Randomized, Placebo-Controlled, Double-Blind, Pilot Study of CCR5/CCR2 Inhibitor Cenicriviroc (CVC) for HIV Associated Neurocognitive Disorder (HAND). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 4, 2013. NLM Identifier: NCT02128828. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02128828. Last accessed on October 13, 2016.
- Tobira Therapeutics website. Cenicriviroc. Available at: http://www.tobiratx.com/pipeline/cenicriviroc/. Last accessed on October 13, 2016.
- Briz V, Poveda E, Soriano V. HIV entry inhibitors: mechanisms of action and resistance pathways. J Antimicrob Chemother. 2006 Apr;57(4):619-27. Available at: http://jac.oxfordjournals.org/content/57/4/619.long. Last accessed on October 13, 2016.
- Marier JF, Trinh M, Pheng LH, Palleja SM, Martin DE. Pharmacokinetics and Pharmacodynamics of TBR-652, a Novel CCR5 Antagonist, in HIV-1-Infected, Antiretroviral Treatment-Experienced, CCR5 Antagonist-Naïve Patients. Antimicrob Agents Chemother. 2011 Jun;55(6):2768-74. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101382/. Last accessed on October 13, 2016.
- Klibanov OM, Williams SH, Iler CA. Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection. Curr Opin Investig Drugs. 2010 Aug;11(8):940-50. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20721836. Last accessed on October 13, 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 October 13, 2016.
- Thompson M, Saag M, DeJesus E, et al. A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus. AIDS. 2016 Mar 27; 30(6): 869-78. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794136/pdf/aids-30-869.pdf. Last accessed on October 13, 2016.
- Tobira Therapeutics: News, dated October 17, 2013. Tobira Therapeutics Presents Positive 48-Week Data from Phase 2b Trial of Cenicriviroc in Treatment-Navie HIV Infection at the 14th European AIDS Conference. Available at: http://files.shareholder.com/downloads/AMDA-2VQ912/2836889662x0x770942/A350DD2A-7061-40A6-BDD1-8B6E4986A158/770942.pdf. Last accessed on October 13, 2016.
- Feinberg J, Thompson M, Cade J, et al. Final Week 48 Analysis of Cenicriviroc (CVC) Compared to Efavirenz (EFV), in Combination with Emtricitabine/Tenofovir (FTC/TDF), in Treatment-Naïve HIV-1-Infected Adults with CCR5-Tropic Virus (Study 652-2-202; NCT01338883). 14th European AIDS Conference; October 16-19, 2013; Brussels, Belgium. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/EACS/EACS_10.htm. Last accessed on October 13, 2016.
- Feinberg J, Thompson M, Cade J, et al. Final Week 48 Analysis of Cenicriviroc (CVC) Compared to Efavirenz (EFV), in Combination with Emtricitabine/Tenofovir (FTC/TDF), in Treatment-naïve HIV-1-infected Adults with CCR5-Tropic Virus. Abstract presented at: 14th European AIDS Conference; October 16-19, 2013; Brussels, Belgium. Abstract PS4/1. Available at: http://www.professionalabstracts.com/eacs2013/planner/index.php?go=abstract&action=abstract_iplanner&print=0&lprID=142&highlight=cenicriviroc&PSID=AOLYUNDFJHCSEFPDLAAC. Last accessed on October 13, 2016.
Last Reviewed: October 13, 2016