KENILWORTH, N.J., Sept. 17 Schering-PloughCorporation (NYSE: SGP) today announced that it has initiated two large PhaseIII clinical studies with vicriviroc, its investigational CCR5 antagonist,administered once-daily as a single 30 mg tablet in combination with anoptimized background therapy that must include a protease inhibitor boosted byritonavir in adult treatment-experienced HIV patients with R5-type virus only.Vicriviroc is a next-generation extracellular inhibitor of HIV infectiondesigned to block entry of infectious virions into uninfected CD4 cells viaantagonism of the CCR5 co-receptor.
The vicriviroc Phase III clinical program builds upon previous studies inHIV treatment-experienced patients, including a Phase II study (ACTG 5211) inwhich vicriviroc demonstrated potent and sustained viral suppression through48 weeks of therapy.(1)
The two Phase III studies, known as VICTOR-E3 and VICTOR-E4 (Vicriviroc inCombination Treatment with an Optimized Antiretroviral Therapy Regimen in HIV-Infected Treatment-Experienced Subjects), will evaluate the virologic benefitof adding vicriviroc 30 mg once daily to an optimized background therapycompared to a control group receiving new optimized background therapy alone.The studies will also evaluate the safety and tolerability of vicriviroccompared to placebo. The optimized background therapy must include at leasttwo drugs that are active, based on susceptibility testing. Patientscoinfected with hepatitis C may be included in the studies and there are noexclusions of commonly prescribed drugs or need for dose adjustments based onthe known vicriviroc drug-drug interaction profile. The studies will enrollapproximately 375 patients each at more than 160 sites in North America, SouthAmerica, Europe, Australia and South Africa.
"As a next-generation HIV entry inhibitor, vicriviroc has the potential tobenefit a broad range of patients by offering a potent, sustained viralresponse and a single once-daily dose in combination with optimized backgroundtherapy," said Robert J. Spiegel, M.D., chief medical officer and senior vicepresident, Schering-Plough Research Institute. "There is an urgent need fornew antiretroviral agents with novel mechanisms of action and we look forwardto the further clinical evaluation of vicriviroc in these large globalstudies."
About the VICTOR-E3 and VICTOR-E4 Phase III Studies
VICTOR-E3 and VICTOR-E4 are identically designed, randomized, double-blind, placebo-controlled, parallel group, multicenter studies of vicrivirocin adult treatment-experienced patients infected with CCR5-tropic HIV virus(no detectable CXCR4-tropic or dual/mixed CCR5/CXCR4-tropic virus atscreening).
The primary efficacy endpoint of the studies will be the proportion ofpatients with plasma HIV-1 RNA less than 50 copies/mL at week 48. Keysecondary endpoints, each measured at 48 weeks, include the proportion ofpatients with less than 400 copies/mL of plasma HIV-1 RNA, mean change frombaseline in plasma HIV-1 RNA (log10 copies/mL) and mean change from baselineCD4+ count. All efficacy endpoints will also be evaluated at week 24.
Patients in VICTOR-E3 and VICTOR-E4 must have documented resistance to atleast two of the three antiretroviral drug classes (NRTI, NNRTI or PI)(2-4) or6 months or more of experience with at least two of the following: one NRTI,one NNRTI or two PIs (excluding low-dose ritonavir); and must have plasma HIV-1 RNA levels above 1000 copies/mL. The optimized background therapy mustinclude a protease inhibitor boosted by ritonavir and at least two drugs thatare active, based on susceptibility testing. The optimized background therapywill be chosen by the investigator based on results of drug susceptibilitytests performed at screening, patient history of prior antiretroviral drug useand drug toxicity.
The VICTOR-E3 and VICTOR-E4 studies will also ev