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DUET-2: 24 week results of a phase III randomised double-blind trial to evaluate the efficacy and safety of TMC125 versus placebo in 591 treatment-experienced HIV-1 infected patients
Presented by Christine Katlama, France.
Katlama C.1, Campbell T.2, Clotet B.3, Johnson M.4, Lazzarin A.5, Arasteh K.6, Towner W.7, Trottier B.8, Peeters M.9, Vingerhoets J.9, De Smedt G.9, Baeten B.9, Beets G.9, Sinha R.9, Woodfall B.9, on behalf of the DUET-2 study group
1Hôpital Pitié-Salpêtrière, Paris, France, 2University of Colorado Health Sciences Center, Denver, United States, 3Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, UAB, Barcelona, Catalonia, Spain, 4Royal Free Hospital, London, United Kingdom, 5Vita-Salute, San Raffaele University, Milan, Italy, 6Epimed, c/o Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany, 7Kaiser Permanente, Los Angeles, CA, United States, 8Clinique Médicale l'Actuel, Montréal, Quebec, Canada, 9Tibotec BVBA, Mechelen, Belgium
Background: TMC125 (etravirine, ETR) is a next-generation NNRTI.
Methods: DUET-2 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, NRTI(s) and optional enfuvirtide. Eligible subjects had documented NNRTI resistance and ³3 primary PI mutations at screening. Primary analysis 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 591 patients. Baseline median VL 4.8 log10; CD4 cell count 105, 55% CDC Category C, median NNRTI mutations 2. Enfuvirtide used de novo by 27%. Week 24 efficacy:
| | TMC125 group | Placebo group | Diff (95% CI) | | <50 copies/ml | 62% | 44% | 18% (11%; 26%)* | | <400 copies/ml | 75% | 54% | 21% (14%; 29%)* | | Mean (SE) change in viral load (log10) | –2.34 (0.076) | –1.68 (0.081) | 0.510^ (0.276; 0.743)** | | Mean (SE) change in CD4 cell count | 78.1 (4.87) | 65.5 (4.72) | 6.590^ (-7.814; 20.994) | | SE: standard error. ^LSmeans difference. *p<0.001 logistic regression model. **p<0.0001 ANCOVA model |
TMC125 was also superior over placebo in the subgroup of patients re-using or not using enfuvirtide. For TMC125 and placebo groups, respectively, incidences of serious AEs, Grade 3/4 AEs and AEs leading to discontinuation were comparable: 15% vs 17%, 29% vs 27% and 6% vs 4%. Most common AEs were diarrhea (18% vs 20%), nausea (14% vs 10%), rash (any type) (14% vs 9%). Rashes were usually mild to moderate and infrequently required discontinuation (2.4%). No clinically relevant changes in laboratory parameters were noted.
Conclusions: TMC125 is the first NNRTI to demonstrate significant and sustained antiviral benefit at 24 weeks in patients with NNRTI resistance. TMC125 is generally safe and well tolerated, with a side effect profile similar to placebo.
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