 |
|
|
| |
TNX-355, New HIV Drug, at ICAAC
|
| |
| |
Reported by Jules Levin
ICAAC Dec 18, 2005, Wash DC
Several points. TNX-355 is intravenously administered by infusion and this study examines two different dosing regimens. This phase II study looks at triple-ART experienced patients who were administered one of 2 dose regimens of TNX-355 + Optimized Background Regimen or only OBR. There were 27 patients in each of the three study arms. Viral load reductions after 24 weeks were about 1 log in the study patients receiving TNX-355 vs -0.25 on the OBR arm.
The information in this report comes from the poster at ICAAC. The baseline characteristics reported were not very detailed excluding prior ART experience. There is no mention of T20 use in the study or what drugs were used in the OBR. Side effects & safety profile of study patients after taking TNX-355 is not detailed, except to report a low rate of adverse events. See tables below. Five serious adverse events were reported and study authors reported none were study drug related --
--Bradycardia on day 1: resolved; continued study therapy.
--liver failure at week 24: discontinued study therapy, stabilized.
--maculopapular rash at week 1: discontinued study therapy, resolved.
--depression and episode of acute abdominal pain at week 8: resolved, continued study.
--acute renal failure at week 10: resolved, continued study.
ABSTRACT
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 once weekly for 8 wks followed by 10mg/kg every 2 wks; 15 mg/kg every 2 wks, or placebo. In addition, all patients were treated with OBR (optimized background regimen). 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 ≥1 infusion), was analyzed. Statistical tests were corrected for multiple comparisons of each TNX-355 containing arm versus OBR alone.
Subjects were sensitive to one or more antiretroviral agents as determined by the PhenoSense GT.
Subjects were failing current HAART regimen or discontinued failing HAART within 8 weeks prior to screening.
AUTHOR CONCLUSIONS
TNX-355 10 mg/kg + OBR demonstrated a 0.96 log10 greater reduction in HIV-RNA than placebo + OBR (1.16 log10 vs. 0.2 log10) at 24 weeks (p<0.001).
TNX-355 15 mg/kg + OBR demonstrated a 0.75 log10 greater reduction in HIV-RNA than placebo + OBR (0.95 log10 vs. 0.2 log10) at 24 weeks (p=0.003).
TNX-355 10 mg/kg + OBR demonstrated in 22% of patients with <400 copies/mL at 24 weeks while no patients were <400 copies/mL in the placebo + OBR group (p=0.02).
Both dosages of TNX-355 demonstrated statistically superior viral load reduction by area under curve minus baseline (AAUCMB) and time to virologic failure through Week 24.
Both dosages of TNX-355 were well tolerated with no injection-site reactions were reported.
No CD4+ cell depletion was observed.
Five serious adverse events (SAEs) were reported with none of these events related to study drug.
Good patient adherence to study visits and acceptance of IV administration.
Week 24 efficacy results demonstrate significant antiviral activity and warrants continued development of TNX-355 in treatmentexperienced HIV positive patients.
Results:
summary of efficacy data at week 24:
|
|
| |
| |
|
|
|
|
|
