Gilead Sciences, Inc. has announced that it has begun enrolling patients in a Phase III clinical trial of its investigational antiretroviral agent elvitegravir (GS 9137), a novel oral integrase inhibitor that is being evaluated for the treatment of HIV-1 infection.
The study is designed to assess the non-inferiority of ritonavir-boosted elvitegravir, dosed once daily, compared to raltegravir (Isentress), another integrase inhibitor that is dosed twice daily. The study will enroll 700 HIV-infected, treatment-experienced patients at approximately 125 sites in the United States and Puerto Rico. A second Phase III study with a similar design involving 700 HIV-infected, treatment-experienced patients will be initiated later this year in Europe, Canada and Australia.
"Advancing novel compounds for the treatment of HIV/AIDS remains a key area of focus for Gilead, and we are very pleased that our integrase inhibitor, elvitegravir, continues to make progress with the initiation of this Phase III clinical trial," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "As HIV patients remain on therapy for longer periods of time, the development of resistance to existing classes of drug is a significant concern. Based on the results observed in our Phase II study of elvitegravir, we believe the compound may have the potential to play an important role for patients in need of new treatment options."
Unlike other classes of antiretroviral agents, integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells.
The elvitegravir Phase III study is a randomized, double-blind, 48-week clinical trial that will assess the non-inferiority of ritonavir-boosted elvitegravir (n=350) versus raltegravir (n=350), each administered with a background regimen in HIV-infected treatment-experienced adults with HIV RNA (viral load) of ¡Ý1,000 copies/mL. Patients will have documented viral resistance, as defined by International AIDS Society-USA guidelines, or at least six months of treatment experience with two or more different classes of antiretroviral agents prior to screening. Patients who have previously taken an integrase inhibitor will be excluded.
Trial participants will receive either once-daily elvitegravir 150 mg or twice-daily raltegravir 400 mg. Patients' background regimens will be based on the results of resistance testing and will include a fully-active ritonavir-boosted protease inhibitor (PI), and a second agent that may be a nucleoside reverse transcriptase inhibitor (NRTI), etravirine, maraviroc or enfuvirtide. Due to known pharmacokinetic interactions, elvitegravir patients whose background PI is either atazanavir or lopinavir will receive an 85 mg dose of elvitegravir.