Phase 2 efficacy and safety of the novel entry inhibitor, TNX-355, in combination with optimized background regimen (OBR)
Background: TNX-355 is a novel humanized monoclonal antibody that binds to domain 2 of the CD4 receptor, blocking entry of HIV-1 into target cells. A 24-week (wk) interim assessment of the ongoing 48-wk randomized, double blind, placebo controlled Phase 2 study was conducted.
Methods: Triple-class experienced HIV-1 infected patients were randomized to receive TNX-355 intravenously: 10mg/kg Q wk for 8 wks followed by 10mg/kg Q 2 wks; 15 mg/kg Q 2 wks, or placebo. In addition, all patients were treated with OBR. Upon experiencing virologic failure (< 0.5 log10 drop from baseline [BL] after week 16), participants receive open-label TNX-355 in combination with new OBR. The primary endpoint was the mean change in HIV-RNA (VL) from BL at wk 24. A modified intent-to-treat (mITT) population (received ³ 1 infusion), was analyzed. Statistical tests were corrected for multiple comparisons of each TNX-355 containing arm versus OBR alone.
82 patients (87% male, 46% white) enrolled: mean age 46 years. Summary of WK 24 Data
|TNX-355||15mg/kg+OBR n=28||10mg/kg+OBR n=27||Placebo + OBR n=27|
|Mean VL change log 101||–0.95 (p=0.003)||–1.16 (p<0.001)||–0.20|
|N (%) ³1.0 log10 reduction||10 (36)||12 (44)||6 (22)|
|N (%) ³0.5 log10 reduction||14 (50) (p=0.050)||15 (56) (p=0.024)||6 (22)|
|AAUCMB||-0.97 (p=0.001)||-1.20 (p<0.001)||-0.41|
|N (%) <400 copies/mL ||2 (7)||6 (22) (p=0.02)||0 (0)|
|Median time to virologic failure (days)||NE2||NE2||86|
|Mean change in CD4+ (cells/mL)||51 ||9||5|
|Mean change from BL CD4 (BL CD4 <200)||33 (p=0.008)||7||-15|
|CD4 AUC through Wk 24||81 (p=0.035) ||46||17|
1NC=LOCF, the mean of last two values imputed for Wk 24
2NE=Not estimated (median failures not reached at WK 24)
Conclusions: TNX-355 in combination with OBR versus OBR alone produced greater antiviral activity in triple-class experienced patients with limited therapy options.
AIDS 2006 - XVI International AIDS Conference
"D.Norris, et al.
Phase 2 efficacy and safety of the novel entry inhibitor, TNX-355, in combination with optimized background regimen (OBR).
AIDS 2006 - XVI International AIDS Conference: