International AIDS Society


Abstract



Phase 2 efficacy and safety of the novel entry inhibitor, TNX-355, in combination with optimized background regimen (OBR)

D. Norris1, J. Morales2, J. Gathe3, E. Godofsky4, F. Garcia5, R. Hardwicke6, S. Lewis7

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.

Results:
82 patients (87% male, 46% white) enrolled: mean age 46 years. Summary of WK 24 Data


TNX-35515mg/kg+OBR n=2810mg/kg+OBR n=27Placebo + OBR n=27
Mean VL change log 101–0.95 (p=0.003)–1.16 (p<0.001)–0.20
N (%) ³1.0 log10 reduction10 (36)12 (44)6 (22)
N (%) ³0.5 log10 reduction14 (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)NE2NE286
Mean change in CD4+ (cells/mL)51 95
Mean change from BL CD4 (BL CD4 <200)33 (p=0.008)7-15
CD4 AUC through Wk 2481 (p=0.035) 4617
[ ]

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
Abstract no. TUPE0058


Suggested Citation
"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: Abstract no. TUPE0058"