Phase II, Randomized, Double-Blind Study of the Safety and Efficacy of Vicriviroc (An Orally Administered HIV-1 Entry Inhibitor) in HIV-Infected, Treatment-Experienced Subjects

Vicriviroc is an oral HIV-1 entry inhibitor that targets the CCR5 receptor of T cells. Vicriviroc has been shown safe, well-tolerated, and active in Phase I clinical trials in treatment-naive HIV infected patients. The goal of this study is to evaluate the antiretroviral activity of three dose levels of vicriviroc in HIV infected, treatment-experienced patients who are failing their current ritonavir-containing antiretroviral therapy (ART).

The study will last at least 48 weeks, but no more than 5 years. There are 3 steps in this study. Patients will be randomly assigned to one of 4 groups. Group 1 will receive placebo; Group 2 will receive 5 mg vicriviroc daily; Group 3 will receive 10 mg vicriviroc daily; and Group 4 will receive 15 mg vicriviroc daily. If at or after Week 16 a participant's viral load has not met certain criteria, a dose increase of vicriviroc may occur and the participant will enter Step 2. As of 10/12/05, patients in Group 2 and any patients who entered Step 2 following virologic failure in Step 1 will be unblinded and offered either 15 mg vicriviroc daily through this study or the option of seeking alternative treatment. All patients will continue their current ART (not provided by the study). After two weeks, patients will receive ART optimized by the results of genotypic/phenotypic testing performed at study screening. All participants who have received or are receiving vicriviroc will enter Step 3 and be followed for an additional 4 years. Participants who complete the study may be eligible to receive vicriviroc through a rollover study sponsored by Schering-Plough, the drug's manufacturer.

Physical exams and blood collection will occur at study entry, Day 4, and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood will be drawn twice, at least 2 hours apart, at both Weeks 2 and 8 for vicriviroc pharmacokinetic analysis. Patients will undergo an electrocardiogram (EKG) at Weeks 2, 8, 24, and 48. Patients will be assessed for peripheral neuropathy at study entry and Weeks 24 and 48, and will be asked to complete an adherence questionnaire at entry and Weeks 2, 8, 16, 24, 32, 40, and 48. For Step 3 participants undergoing follow-up, physical exams and blood work will occur every 6 months for 4 years.

Five participants currently enrolled at four sites that are no longer receiving funding and who will not be transferred or redirected to a site within their proximity will be subject to the following changes. There will no longer be follow-up visits per the schedule of events described in the protocol. Instead, participants will have their follow-up limited to self-report through telephone interviews to ascertain vital status, occurrence of malignancies (if any), and collection of information such as HIV-1 RNA and CD4 cell count. For these participants only, the HIV-1 RNA and CD4 cell count will be done as part of the participant's clinical care and will not be paid for by the study. The follow-up telephone interviews will be conducted at six-month intervals using the script provided by the study team.