C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis

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Presentation transcript:

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis ARV-trial.com C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis Design Randomisation 1 : 1 Open-label W8 W12 W16 EBR/GZR + SOF + RBV Naive ≥ 18 years Chronic HCV infection Genotype 3 Treatment-naïve or PEG-IFN experienced Compensated cirrhosis** No HBV co-infection EBR/GZR + SOF EBR/GZR + SOF Experienced* EBR/GZR + SOF + RBV EBR/GZR + SOF ** Liver biopsy or Fibroscan > 12.5 kPa * Randomisation of treatment-experienced patients was stratified on prior relapse vs non relapse (partial, null, interferon-intolerant) EBR/GZR 50/100 mg 1 tablet QD ; SOF 400 mg QD ; RBV 800-1400 mg/day Objective Primary endpoint: SVR12 (HCV RNA < 15 IU/mL), full analysis set (patients who received ≥ 1 dose of study drug) C-ISLE Foster GR. AASLD 2016, Abs. 74 1

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis ARV-trial.com C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis Baseline characteristics Genotype 3 with cirrhosis N = 100 Mean age, years 53.4 Female, % 32 Race : white / asian % 69 / 29 Fibroscan® score, mean kPa 25.4 + 12.1 HCV RNA log10 IU/mL, mean 6.2 IL28B CC, % 50 Prior treatment history, % Naive PEG-IFN experienced 47 53 Platelets x 103/mm3, mean < 100 x 103/mm3, % 148 24 C-ISLE Foster GR. AASLD 2016, Abs. 74 2

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis SVR12 (FAS), % Treatment-naive Treatment-experienced % 100 96* 100 91 94* 94* 75 50 25 n 23 23 17 18 18 EBR/GZR + SOF + RBV (8 weeks) EBR/GZR + SOF (12 weeks) EBR/GZR + SOF (12 weeks) EBR/GZR + SOF + RBV (12 weeks) EBR/GZR + SOF (16 weeks) Relapse 2 Non virologic failure 1* 1** 1*** * SVR12 = 100% in mFAS analysis, excluding patients who discontinued treatment for reasons unrelated to study medication (* lost to follow-up, ** consent withdrawal, *** discontinuation at D7 for cellulitis) C-ISLE Foster GR. AASLD 2016, Abs. 74

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis ARV-trial.com C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis Resistance data SVR12 according to baseline NS5A RAVs (15% sensitivity threshold): NS5A polymorphisms at positions 24, 28, 30, 31, 32, 38, 58, 62, 92, or 93) 98% (48/49) if RAVs 98% (46/47) if no RAVs If Y93H present (N = 4): SVR12 = 0/1 (relapse) if 8 weeks treatment ; 3/3 (100%) if > 8 weeks treatment 2 relapses Both patients received EBR/GZR/SOF + RBV for 8 weeks No NS5A RAVS at baseline or failure in 1 patient In 1 patient : NS5A RAVs at baseline : Y93H, P58, S62T ; at failure : P58 and S62T C-ISLE Foster GR. AASLD 2016, Abs. 74 4

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis ARV-trial.com C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis Adverse events EBR/GZR + SOF + RBV 8 weeks N = 23 EBR/GZR + SOF 12 weeks N = 41 N = 18 16 weeks Drug-related adverse event, % Fatigue Nausea Skin rash/pruritus 13 17.4 8.7 22.0 9.8 7.3 50.0 27.8 44.4 16.7 11.1 Serious adverse event, N (%) * 1 (2.4) 3 (16.7) 1 (5.6) Discontinuation due to adverse event, N (%) 1 (5.6) ** Laboratory abnormalities, % Hemoglobin < 10 g/dL Total bilirubin > 5 x baseline AST/ALT > 5 x ULN 2.4 * Lung infection, creatinine increased, chest pain, opiate overdose, and cellulitis ** 1 patient discontinued treatment at Day 7 due to cellulitis C-ISLE Foster GR. AASLD 2016, Abs. 74 5

C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis ARV-trial.com C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis Summary High efficacy was demonstrated in treatment-naive and treatment-experienced cirrhotic HCV genotype 3-infected patients There were no virologic failures among patients receiving EBR/GZR + SOF + RBV for 12 or 16 weeks Treatment duration longer than 12 weeks is not needed High efficacy was seen regardless of presence of baseline NS5A RAVs or patient characteristics Generally safe and well tolerated C-ISLE Foster GR. AASLD 2016, Abs. 74 6