Design W12 Randomisation * Open-label

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Presentation transcript:

TRILOGY-3 Study: SOF/VEL/VOX ± RBV in DAA-experienced patients - Phase II Design W12 Randomisation * Open-label > 18 years Chronic HCV infection Genotype 1 HCV RNA ≥ 10 000 IU/ml DAA-experienced for ≥ 6 weeks Compensated cirrhosis allowed (around 50%) No HBV or HIV co-infection N = 24 SOF/VEL/VOX SVR12 SOF/VEL/VOX + RBV SVR12 N = 25 * Randomisation was stratified by cirrhosis (yes or no) and NS5A inhibitor experience (yes or no) SOF/VEL/VOX: 400/100/100 mg FDC qd RBV : 1000 or 1200 mg/day, according to body weight Objective SVR12 (HCV RNA < 15 IU/ml), by ITT, with 95% CI TRILOGY-3 Lawitz E. Hepatology 2017; 65:1803-9

TRILOGY-3 Study: SOF/VEL/VOX± RBV in DAA-experienced patients - Phase II Baseline characteristics and outcome SOF/VEL/VOX N = 24 SOF/VEL/VOX + RBV N = 25 Age, years, mean 54 Female, % 33 36 White, % 71 88 HCV RNA, log10 IU/ml, mean 6.2 6.3 IL28B CC, % 8 20 Cirrhosis, % 46 52 Genotype 1a, % NS5A inhibitor experienced, % 42 40 Baseline RASs (1% threshold) 35/48 (73%) ; NS5A only = 15% ; NS3 only = 31% ; multiple class = 27% SVR12 100% 96% (1 relapse) Relapse: 61y, black, male, cirrhosis, IL28B CC, prior treatment with LDV/SOF 24 weeks ; HCV RNA < LLOQ from Day 7 to end of treatment with SOF/VEL/VOX, relapse at W4 post-treatment At baseline of SOF/VEL/VOX At failure NS5A RASs M28V (1.7%), Q30H (3.2%), L31M (> 99%) M28T (> 99%), Q30L (2.4%), Q30R (97.3%), L31M (> 99%) NS3 RASs None V36M (> 99%), Q41R (> 99%), D168G (96.4%), D168S (2.4%) NS5B RASs TRILOGY-3 Lawitz E. Hepatology 2017; 65:1803-9

TRILOGY-3 Study: SOF/VEL/VOX ± RBV in DAA-experienced patients - Phase II Adverse events and laboratory abnormalities % SOF/VEL/VOX SOF/VEL/VOX+ RBV Any adverse event 46 60 Grade 3-4 adverse event 4 (N = 1, grade 3 rash, RBV discontinuation) Serious adverse event 4 Discontinuation for adverse event Adverse events in ≥ 5% of patients Fatigue 36 Anemia 16 Diarrhea 13 Gastroenteritis 8 Bronchitis Nausea Hemoglobin 8.5-10 g/dl ; < 8.5 g/dl 24 / 8 TRILOGY-3 Lawitz E. Hepatology 2017; 65:1803-9

TRILOGY-3 Study: SOF/VEL/VOX± RBV in DAA-experienced patients - Phase II Summary SOF/VEL/VOX once daily ± RBV for 12 weeks achieved high SVR12 rate in HCV genotype 1-infected patients with prior DAA experience Addition of RBV did not enhance SVR Baseline RASs did not reduce SVR SVR12 = 13/13 (100%) if no baseline RASs vs 34/35 (97%) if baseline RASs The combination was generally well tolerated Adverse event profile was less good with RBV TRILOGY-3 Lawitz E. Hepatology 2017; 65:1803-9