39LB
Vicriviroc, a Next Generation CCR5 Antagonist, Exhibits Potent, Sustained Suppression of Viral Replication in Treatment-experienced Adults: VICTOR-E1 48-week Results
Barry Zingman*1, J Suleiman2, E DeJesus3, J Slim4, M McCarthy5, E Lee5, N Case5, C Mak5, and L Dunkle5
1Montefiore Med Ctr, Bronx, NY, US; 2Brazilmed Assistencia Medica e Pesquisa, Sao Paolo; 3Orlando Immunology Ctr, FL, US; 4St Michael`s Med Ctr, Newark, NJ, US; and 5Schering-Plough Res Inst, Kenilworth, NJ, US
Background: Vicriviroc (VCV) is a potent CCR5
antagonist with predictable pharmacokinetics dosed once daily with a ritonavir (RTV)-boosted
protease inhibitor (PI) -containing regimen. Sustained efficacy was shown previously
with 10 and 15 mg once daily.
Methods: VICTOR E-1, a double-blind trial, compared VCV
20 and 30 mg once daily to placebo in CCR5-tropic HIV patients experienced with
≥3 classes of ART. Subjects had HIV RNA ≥1000 copies/mL despite
stable ART for ≥6 weeks. VCV was dosed with a new RTV-boosted,
PI-containing optimized background therapy (OBT) containing ≥3 drugs. The
primary endpoint was change in HIV RNA at week 48. Secondary endpoints included
% achieving <400 and <50 copies/mL.
Results: Of 116 subjects, 78% were male, 68%
Caucasian, 71% Latino, and 5% HIV/hepatitis C virus (HCV) co-infected. Mean
baseline HIV RNA was 4.5, 4.5, and 4.6 log10 copies/mL in the VCV 30
mg, 20 mg, and placebo arms, respectively. Mean baseline CD4 counts were 202,
202, and 226 cells/mm3. Of the total, 33 (85%), 35(88%), and 18(49%)
completed the study in the 3 groups. Mean HIV RNA declines at week 48 were –1.77,
–1.75, and –0.79log10, respectively. Mean CD4 changes at week 48
were +102, +136, and +63 cells/mm3. Emergence of detectable X4
tropic HIV occurred mostly in the first 8 weeks of treatment and did not
necessarily coincide with virologic failure. There were no apparent dose or
drug-related toxicities. Most treatment-emergent adverse events were evenly
distributed across treatment arms. Cmin
at 30 mg was above the 100 ng/mL threshold in almost all subjects, supporting
this dose.
|
Intent-to-treat analysis (all
treated subjects)
|
VCV 30
mg once daily +
OBT
(n = 39)
|
VCV 20 mg once
daily +
OBT
(n = 40)
|
Placebo +
OBT
(n = 35)
|
|
%<50 copies/mL
(p value vs placebo)
|
22 (56%)
(0.0002)
|
21(52%)
(0.0004)
|
5 (14%)
|
|
Subset analyses
|
Subjects <50
copies/mL
|
|
Baseline RNA ≥100,000
Baseline RNA
<100,000
|
4/12 (33%)
18/27 (67%)
|
2/12 (17%)
19/28 (68%)
|
1/10 (10%)
4/25 (16%)
|
|
DRV-containing
OBT n (%)
|
9/12 (75%)
|
6/9 (67%)
|
2/6 (33%)
|
|
#active drug(s)
in OBT:
≥3
1-2
0
|
*OSS missing at baseline 3 subjects
5/7 (71%)
14/22 (64%)
2/7 (29%)
|
5/6 (83%)
15/26 (58%)
1/8 (12%)
|
0/6 (0%)
5/22 (23%)
0/7 (0%)
|
|
% Patients
with/Cmin >100 ng/mL
|
92%
|
82%
|
0
|
|
Safety analyses
|
|
|
Virologic failure
|
5 (18)
|
3 (8)
|
14 (40)
|
|
Emergence detectable
X4 virus
|
9 (23)
|
7 (10)
|
3 (9)
|
|
Grade 3/4 adverse events n(%)
|
8/39 (21%)
|
8/40 (20%)
|
7/35 (20%)
|
Conclusions: VCV 30
or 20 mg once daily plus RTV-containing OBT provided sustained viral
suppression in treatment-experienced
subjects and increased CD4
cell counts regardless of the # of active drugs in OBT. VCV 30 mg showed superior
efficacy based on % fully suppressed (<50 copies/mL) and was well tolerated. Phase 3
trials are ongoing.
|
