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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-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
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"
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