1 / 9

N = 75

ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease. Design. Randomisation* 1 : 1 : 1 Open-label. W12. W24. > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or NS5B inhibitor Child-Pugh B cirrhosis **

brook
Download Presentation

N = 75

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • Design Randomisation* 1 : 1 : 1 Open-label W12 W24 > 18 years Chronic HCV infectionGenotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or NS5B inhibitor Child-Pugh B cirrhosis ** No hepatocellular carcinoma No liver transplantationCreatinine clearance > 50 ml/min Platelets > 30,000/mm3 N = 75 SVR12 N = 75 N = 75 SVR12 * Randomisation was stratified on HCV genotype ** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest > 0.75 and APRI > 2 • RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) • Objectives • SVR12 (HCV RNA < 15 UI/ml) with 2-sided 95% CI, by ITT, 99% power to detect a SVR12 ≥ 41% ;not powered to detect significant differences in SVR among the treatment groups • Changes in MELD and CPT scores ASTRAL-4 Curry MP. N Engl J Med 2015; 373: 2618-28

  2. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • Baseline characteristics and patient disposition Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  3. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • SVR12, % (95% CI) SOF/VEL + RBV 12W SOF/VEL 12W SOF/VEL 24W 100 (77-100) % 100 100 94 (87-98) 94 (85-99) 93 (82-98) 100 89 (65-99) 88 (76-96) 88 (62-98) 85 (55-98) 86 (77-92) 83 (74-90) 86 80 60 50 (23-77) 50 (21-79) G2 4 4 4 40 2 2 G4 4 20 1 G6 90 87 90 50 54 55 18 14 16 14 13 12 0 Overall Genotype 1a Genotype 1b Genotype 3 Genotype 2, 4, 6 Breakthrough, N Relapse, N LTFU, N Death, N - 11 1 3 - 2 - 2 1 7 3 2 - - - - - - - - - - - - - - - - - - - - - - - - - 6 - 1 1* 1 - - 1 4 - 1 - - - - - - - - - - - 1 *Patient with non-detectable drug levels at time of virological failure, LTFU, lost to follow-up Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  4. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • Characteristics of patients with virologic failure Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  5. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • CPT score change : baseline to follow-up W12 (% of patients) % 60 11% 47% Improved 11% Worsened 50 42 40 32 30 20 12 8 10 2 2 < 1 < 1 < 1 < 1 0 N = 1 1 5 31 79 106 21 4 1 1 Change inCPT score -5 -4 -3 -2 -1 0 1 2 4 5 17/267patients had no follow-up W12 assessment Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  6. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease MELD change: baseline to follow-up W12 (% of patients) % BaselineMELD < 15N = 223 50 51% Improved 27% Worsened 40 30 22 20 20 15 13 10 8 10 4 0 0 2 2 2 1 1 < 1 < 1 0 N = 0 0 3 2 9 4 18 34 44 49 30 22 2 4 1 1 % Change in MELD -11 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 7 11 50 84% Improved 8% Worsened BaselineMELD > 15N = 27 40 30 26 19 20 15 11 7 10 4 4 4 4 4 4 0 0 0 0 0 0 N= 1 1 0 1 2 4 5 1 7 3 1 0 1 0 0 0 Change in MELD -11 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 7 11 17/267patients had no follow-up W12 assessment Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  7. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease Adverse events, N (%) * RBV discontinuation : 17%, dose reduction : 37% Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  8. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease Hematologic abnormalities, N (%) * RBV discontinuation : 17%, dose reduction : 37% Charlton MR, AASLD 2015, Abs. LB13 ; Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

  9. ASTRAL-4 Study: SOF/VEL in patients with decompensated liver disease • Summary • Treatment with SOF/VEL for 12 or 24 weeks or SOF/VEL + RBV for 12 weeks resulted in high SVR12 rates in HCV patients with decompensated cirrhosis caused by HCV of all genotypes • SOF/VEL + RBV resulted in the highest overall SVR12 rates, with the lowest rates of virologic failure in HCV genotype 3 patients • Treatment was associated with improved MELD and CPT scores largely due to decreased bilirubin and improvement in synthetic function (albumin) • SOF/VEL for 12 or 24 weeks or SOF/VEL + RBV for 12 weeks was safe and well tolerated, with adverse events consistent with clinical sequelae of advanced liver disease and RBV toxicity • Limitations • Study not powered to detect significant differences among the 3 treatment groups • Only patients with moderate hepatic decompensation were enrolled • The numbers of patients with HCV genotype 2, 4, or 6 were small • Limited number of black patients Curry MP. N Engl J Med 2015; 373: 2618-28 ASTRAL-4

More Related