Acidosis

Schering-Plough Expands Vicriviroc Phase II Study in Treatment-Naive Patients With HIV

Acidosis Library Library Home This article was published in Anti-Infectives Week, which you can subscribe to online.

The study is being conducted in two stages, with the first stage initiated in January 2008 and having enrolled 95 patients (47-48 per treatment arm). Following 24 weeks of treatment, a formal interim analysis was conducted and the safety results were reviewed by an independent Data Safety Monitoring Board. Based on these results, the study has been extended to stage two, in which the enrollment target is an additional 105 patients.

Unlike other classes of HIV drugs that work to inhibit viral replication within human CD4+ cells, most of which are part of the immune system, vicriviroc is an HIV entry inhibitor designed to prevent the virus from infecting healthy CD4 cells by blocking its predominant entry route, the CCR5 co-receptor. Approximately 80-90 percent of treatment-naive patients have virus that uses the CCR5 co-receptor.(1)

"CCR5 antagonists, such as vicriviroc, have a novel mechanism of action and may play a unique role as physicians seek to construct new HIV regimens to meet the specific needs of their patients," said Joseph C. Gathe, Jr., M.D., F.A.C.P., clinical instructor, department of internal medicine, Baylor College of Medicine, Houston, and lead investigator for the study. "A class-sparing vicriviroc regimen for initial treatment could potentially expand options for patients by offering a new first-line therapy, while having the additional benefit of preserving the current first-line therapy and subsequent regimens for future use."

In the study, the virologic benefit of vicriviroc administered once-daily as a single 30 mg tablet in combination with ritonavir-boosted atazanavir(2) is being compared to a control group receiving Truvada (emtricitabine and tenofovir disoproxil fumarate)(3) plus ritonavir-boosted atazanavir, which is a currently recommended option for first-line therapy. Atazanavir is a product in the protease inhibitor (PI) class of HIV medications. Truvada is a combination product in the nucleoside(tide) reverse transcriptase inhibitor (NRTI) class.

The standard of care for treatment-naive HIV-infected individuals is to combine three drugs from two classes to initiate antiretroviral therapy. The combinations characteristically use two NRTIs with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted PI.(4) While these combinations have been demonstrated to be highly effective, long-term tolerance may be limited by the toxicity specifically associated with nucleosides, which can include neuropathy, myopathy, renal toxicity, hepatic steatosis, lactic acidosis, bone marrow suppression, fat atrophy and, with certain agents, increased risk of myocardial infarction.(5-7)

About the Phase II Naive Study

This randomized, controlled, open-label study is projected to enroll approximately 200 treatment-naive HIV-infected adult patients at more than 35 sites in North America, Central America, Europe and South Africa. Patients coinfected with hepatitis B or C may be included in the study.

The primary efficacy endpoint of the study is the mean change from baseline in viral load (log10 HIV RNA) at week 48 of treatment. A key secondary efficacy endpoint is the proportion of patients with plasma HIV RNA less than 50 copies/mL at week 48 of treatment.

Atazanavir boosted by ritonavir was selected for use in this study because it is recommended as an option for first-line therapy in both the International AIDS Society and Department of Health and Human Services guidelines for antiretroviral therapy. Additionally, like vicriviroc, it is administered as a once daily dose and it has been shown to have a more favorable lipid safety profile than other drugs in the PI class.

The study is being sponsored by Schering-Plough with support from Bristol-Myers Squibb.

Vicriviroc also is being studied in two large ongoing Phase III clinical studies in treatment-experienced HIV patients. For more information about vicriviroc clinical studies, please visit www.clinicaltrials.gov, search term: vicriviroc.

Key Safety Findings with Vicriviroc

A pooled data analysis was conducted for two vicriviroc Phase II studies involving 205 treatment-experienced HIV-infected patients who continued on vicriviroc at the completion of 48 weeks of treatment in an open-label extension for each study. Patients received vicriviroc for up to 216 weeks of total treatment duration as part of an optimized antiretroviral regimen. AIDS-associated opportunistic infections and conditions were observed infrequently and sporadically. Infections involving the upper and lower respiratory tract were the only other infections or adverse events that occurred in 5 percent or more of patients. Elevations of liver enzymes and bilirubin were noted, but were not characteristic of drug-induced liver injury and were judged to be not related to vicriviroc. These infections and other adverse events observed in these patients were generally consistent with expectations for patients with advanced HIV infection and with the multiple drugs being administered.(8)

Keywords: HIV/AIDS, Data Management, Data Safe, Information TechnologyAIDS, Acquired Immunodeficiency Syndrome, Anti-HIV, Antivirals, Atazanavir, Biotechnology Business, Biotechnology Company, Clinical Trial Research, Drug Development, Drugs, Emtricitabine, Enzyme Research, Enzymes, Enzymology, HIV, Human Immunodeficiency Virus, Internal Medicine, Nucleoside Reverse Transcriptase Inhibitor, Nucleoside and Nucleotide Reverse Transcriptase InhibitorsAntiretroviral, Pharmaceutical Business, Pharmaceutical Company, Pharmaceuticals, Protease Inhibitor, Protease Inhibitors, Proteins, Proteomics, Ritonavir, Schering-Plough Corporation, Tenofovir Disoproxil Fumarate, Therapy, Treatment, Truvada, Viral, ViroLogic Inc., Virology.

This article was prepared by Anti-Infectives Week editors from staff and other reports. Copyright 2009, Anti-Infectives Week via NewsRx.com.