105bLB
Results of BENCHMRK-2, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-class Resistant Virus
Ron Steigbigel*1, P Kumar2, J Eron3, M Schechter4, M Markowitz5, M Loufty6, J Zhao7, R Isaacs7, B Nguyen7, H Teppler7, and for the BENCHMRK-2 Study Group
1State Univ of New York at Stony Brook, US; 2Georgetown Univ Med Ctr, Washington, DC, US; 3Univ of North Carolina at Chapel Hill, US; 4Federal Univ of Rio de Janeiro, Brazil; 5Aaron Diamond AIDS Res Ctr, The Rockefeller Univ, New York, NY, US; 6Canadian Immunodeficiency Res Collaborative, Toronto; and 7Merck Res Labs, West Point, PA, US
Background: MK-0518 is a novel and potent HIV-1 integrase
inhibitor, which has no cross resistance to currently approved antiretroviral
drugs.
Methods: BENCHMRK-2 (Protocol 019) is an ongoing
multi-center, triple-blind randomized study to evaluate safety and efficacy of
oral MK-0518 400 mg twice daily vs placebo (2 : 1 randomization), each plus
optimized background therapy (OBT), in HIV-infected patients failing ART with
HIV resistant to 3 classes of oral ART. Patients were enrolled in North,
Central, and South America. Efficacy endpoints
included percentage of patients with HIV RNA <400 and <50 copies/mL and
change from baseline in CD4 cell counts.
Results: Pre-planned 16-week analyses are summarized
in the table. About 60% of patients have completed week 24; data from week 24
also demonstrate superior efficacy of MK-0518 over placebo. MK-0518 was
generally well tolerated with an adverse experience profile similar to placebo.
Conclusions: In this phase III study in patients failing ART with
triple-class resistant HIV, oral MK-0518 400 mg twice daily plus OBT
demonstrated potent and superior antiretroviral effect compared to placebo plus
OBT at week 16 and 24, and was generally well tolerated.
|
BENCHMRK-2
(Protocol 019)
|
MK-0518*
n = 230
|
Placebo*
n = 119
|
Difference
|
|
Baseline
Characteristics: Mean (SD)
|
|
|
|
|
HIV RNA (log10 copies/mL)
|
4.7
(0.8)
|
4.7
(0.7)
|
D MK-0518-Pbo1
|
|
CD4
Cell Count (cells/mm3)
|
146
(143)
|
163
(149)
|
|
|
Efficacy
at Week 16 (95% confidence intervals)
|
|
|
% HIV
RNA <400 copies/mL2
|
77
(71,83)
|
43
(34,52)
|
34
(24,45) %
|
|
% HIV RNA < 50 copies/mL2
|
62
(55,68)
|
36
(28,45)
|
26
(15,36) %
|
|
CD4
Change from Baseline§ (cells/mm3)
|
86 (
72,99)
|
40 (
26,53)
|
46
(27,65) %
|
|
*MK-0518
and placebo were given with OBT
1 Difference between MK-0518 and placebo; a positive value
indicates that MK-0518 was better than pbo
2 Non-completer = failure
§ Baseline values carried forward
for virologic failures
% Nominal p <0.001
|
|
