Tobira Recruiting for Trial of CCR2/CCR5 Entry Inhibitor Cenicriviroc

Tobira Therapeutics has initiated a clinical trial to test its investigational CCR2/CCR5 antagonist HIV entry inhibitor cenicriviroc (TBR-652).

Like maraviroc (Selzentry), cenicriviroc prevents HIV from attaching to the CCR5 coreceptor, which most types of the virus use to enter CD4 T-cells. In addition, cenicriviroc also blocks the CCR2 receptor, suggesting that it may be able to decrease inflammation. Excessive immune activation and inflammation have been implicated in a host of non-AIDS conditions affecting people with HIV, including cardiovascular disease and neurocognitive problems.

In an earlier study cenicriviroc demonstrated potent antiretroviral activity, reducing HIV viral load by as much as 1.8 log when used as monotherapy for 14 days. Levels of monocyte chemoattractant protein 1 (MCP-1, also known as CCL2) increased significantly. MCP-1 is a cytokine that attracts monocytes and macrophages as part of an inflammatory response. Rising levels of MCP-1 in the blood indicates that the cytokine's receptor, CCR2, is blocked.

Study 202 is seeking treatment-naive individuals with viral load > 1000 copies/mL, CD4 count > 250 cells/mm³, and exclusively CCR5-tropic HIV (study investigators will perform this test). The new study will look at measures of inflammation as well as viral suppression and CD4 cell recovery. The trial is enrolling participants at more than 50 sites across the U.S.

Below is an edited excerpt from a study overview provided by Tobira. More information, including Frequently Asked Questions and links to prior research, can be found online at http://www.tobiratherapeutics.com/clincalstudies.php.

Further details are available for the ClinicalTrials.gov website at http://www.clinicaltrials.gov/ct2/show/NCT01338883?term=cenicriviroc&rank=1.

[Editor's note: This article was amended on 11/4/11 to correct an error]

Clinical Trial Overview

Tobira Therapeutics, Inc., a biopharmaceutical company focused on the development and commercialization of innovative therapies for HIV, has initiated a Phase 2b clinical trial of the CCR5/CCR2 inhibitor cenicriviroc (CVC, TBR 652).

Participants in the trial -- CVC Study 202 -- will receive either once-daily 100-mg or 200-mg doses of cenicriviroc in combination with Truvada (emtricitabine/tenofovir disoproxil fumarate, or FTC/TDF), or once-daily Sustiva (efavirenz, or EFV) plus Truvada. The study's primary objectives are to determine the efficacy, safety and tolerability of each CVC regimen versus the comparator regimen. Additionally, several substudies will assess changes in biomarkers associated with inflammation, cardiovascular function, metabolic indicators of glucose control and immune function.

The study lasts for one year and provides study medications at no charge, along with study-related exams and lab tests.

Patient eligibility is based on a number of criteria including but not limited to the following:

• Must be 18 years of age or older
• Must have a viral load of 1,000 copies/mL or higher
• Must have a CD4 count of 250 cells/mm³ or higher, with no CD4 count ever less than 200 cells/mm³
• All study participants must be willing to take appropriate pregnancy-prevention precautions

Patients are not eligible if, among other considerations:

• They have ever been treated for HIV/AIDS in the past
• They have ever had a CD4 count of less than 200 cells/mm³
• They have tuberculosis, hepatitis B or C or cirrhosis of the liver

CVC Study 202 is multicenter study designed to evaluate the efficacy, safety and tolerability of cenicriviroc in HIV-1-infected, antiretroviral treatment-naïve patients with only CCR5-tropic virus. The study is currently recruiting and enrolling 150 adult patients at approximately 50 sites across the United States and Puerto Rico.

To determine if the study is taking place in your city, please refer to the following list of participating sites. As you click on each region, you will be able to see names and locations of specific sites as well as contact information at each site.

http://www.tobiratherapeutics.com/clin_sites.php

9/30/11

Sources

Tobira Therapeutics. http://www.tobiratherapeutics.com/clincalstudies.php.

ClinicalTrials.gov. Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination With Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus. http://www.clinicaltrials.gov/ct2/show/NCT01338883?term=cenicriviroc&rank=1.