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.
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.
D. Norris1, J. Morales2, J. Gathe3, E. Godofsky4, F. Garcia5, R. Hardwicke6, S. Lewis7
1Comprehensive Research Center, Tampa, United States, 2Clinical Research Puerto Rico Inc., San Juan, Puerto Rico, 3Therapeutic Concepts, Houston, United States, 4Bach & Godofsky, Bradenton, United States, 5Valley AIDS Council, Harlingen, United States, 6University of Texas Health Science Center, Houston, United States, 7Tanox Inc., Houston, United States