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DUET-1: 24 week results of a phase III randomised double-blind trial to evaluate the efficacy and safety of TMC125 versus placebo in 612 treatment-experienced HIV-1 infected patients
Presented by Anthony Mills, .
Mills A.1, Cahn P.2, Grinsztejn B.3, Haubrich R.4, Lalezari J.5, Madruga J.V.6, Pialoux G.7, Wilkin T.8, Peeters M.9, Vingerhoets J.9, De Smedt G.9, Leopold L.10, Trefiglio R.10, Woodfall B.9, on behalf of the DUET-1 study group
1Private Practice, Beverly Hills, United States, 2Hospital Juan A. Fernández and Fundación Huesped, Buenos Aires, Argentina, 3Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil, 4University of California San Diego, San Diego, United States, 5Quest Clinical Research, San Francisco, United States, 6Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil, 7Service des Maladies Infectieuses, APHP, Hôpital Tenon, Paris, France, 8Weill Medical College of Cornell University, New York, United States, 9Tibotec BVBA, Mechelen, Belgium, 10Tibotec Inc, Yardley, United States
Background: TMC125 (etravirine, ETR) is a next-generation NNRTI.
Methods: DUET-1 is a 96-week randomised, double-blind phase III trial evaluating the efficacy and safety of TMC125 versus placebo, both given with ART consisting of darunavir/r, investigator-selected NRTI(s) and optional enfuvirtide. Eligible subjects had documented NNRTI resistance and ³3 primary PI mutations at screening. Primary analysis was performed when all patients were treated for ³24 weeks or discontinued earlier. Primary endpoint is proportion with confirmed virologic response (<50 copies/ml) at week 24 (TLOVR imputation algorithm). Safety was assessed throughout the study.
Results: ITT population includes 612 patients. Baseline median VL 4.9 log10; CD4 cell count 106, 62% CDC Category C, median NNRTI mutations 2. Enfuvirtide used de novo by 25%. Week 24 efficacy:
| | TMC125 group | Placebo group | Diff (95% CI) | | <50 copies/ml | 56% | 39% | 17% (9%; 25%)* | | <400 copies/ml | 74% | 51% | 22% (15%; 30%)* | | Mean (SE) change in viral load (log10) | –2.41 (0.074) | –1.70 (0.085) | 0.574^ (0.331; 0.818)** | | Mean (SE) change in CD4 cell count | 89.0 (5.38) | 64.4 (5.22) | 31.740^ (15.236; 48.244) | | SE: standard error. ^LSmeans difference. *p<0.01 logistic regression model. **p<0.0001 ANCOVA model. |
For TMC125 and placebo groups, respectively, incidences of serious AEs, Grade 3/4 AEs and AEs leading to discontinuation were comparable: 12% vs 20%, 21% vs 28% and 5% vs 5%. Most common AEs were diarrhea (12% vs 21%), nausea (14% vs 12%), rash (any type) (20% vs 10%). Rashes were usually mild to moderate and infrequently required discontinuation (1.3%). The incidence of neuropsychiatric events was not different between TMC125 and placebo. No clinically relevant changes in laboratory parameters were noted.
Conclusions: TMC125 is the first NNRTI to demonstrate significant and sustained antiviral benefit at week 24 in patients with NNRTI resistance. TMC125 is generally safe and well tolerated.
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