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W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based.

Published byStewart Hicks Modified over 9 years ago

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Presentation on theme: "W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based."— Presentation transcript:

1 W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based RBV SOF + low-dose RBV Part 2 All stage of fibrosis N = 25 SOF 400 mg : 1 pill qd RBV weight-based : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) RBV low-dose : 600 mg/day Part 1 Early or moderate fibrosis Randomisation 1 : 1 Open-label  Objective –Primary endpoint : SVR 24 (HCV RNA 8 weeks of treatment) –Modelling viral kinetics, pharmacokinetics and pharmacodynamics (20 patients) NIH SPARE Oisinusi A. JAMA 2013;310:804-11  Design NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease

2 Part 1Part 2 SOF + weight- based RBV SOF + low dose RBV N1025 Age, years54 55 Female60%24%44% White / Black10% / 90%20% 72%8% / 92% Genotype 1a / 1b60% / 40%80/ 20%64% / 36% HCV RNA, log 10 IU/ml6.86.26.1 IL 28B CC33%16% Knodell score 0-1 / 3-490% / 10%76% / 24%72% / 28% Discontinuation, N123 NIH SPARE Oisinusi A. JAMA 2013;310:804-11 Baseline characteristics and disposition, median or %

3 SOF + weight-based RBVSOF + low-dose RBV 25 50 100 75 71 (49-87) % 48 (28-69) 75 N2422 50 Per protocol ITTGenotype 1b 68 (46-85) 55 (32-76) 40 44 Genotype 1a 259 52017 Per protocol ITT NIH SPARE Oisinusi A. JAMA 2013;310:804-11 NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease SVR 24 (HCV RNA < 25 IU/ml) in Part 2, % (95% CI) 0

4 Odds ratio95% CIp Men vs women6.11.2 - 31.60.03 BMI > 30 vs ≤ 30 kg/m 2 0.330.1 – 1.20.08 Knodell score 3-4 vs 0-14.31.1 – 16.50.04 HCV RNA > 800,000 IU/ml5.71.4 – 24.40.02 NIH SPARE Oisinusi A. JAMA 2013;310:804-11 NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease Bivariate model of baseline characteristics associated with relapse  Viral kinetic model –No differences in viral decay based on RBV dose or baseline characteristics –Fully fitted PK-viral kinetics model (10 patients on weight-based RBV and 10 patients on low-dose RBV) : significantly slower loss rate of free virus (clearance) in relapsers than participants who achieved SVR (clearance : 3.57 vs 5.60 per day; p = 0.009)

5 NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease NIH SPARE Oisinusi A. JAMA 2013;310:804-11 Histologic response  29 paired liver biopsies –Improvement in inflammation in 27 (93%) 5 10 15 HAI Inflammation score 0 Pre treatment End of treatment Pre treatment End of treatment p = 0.003p < 0.0001 p = 0.07 SOF + weight-based RBV SOF + low-dose RBV

6 NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease Part 1Part 2 SOF + weight- based N = 10 SOF + weight- based RBV N = 25 SOF + low- dose RBV N = 25 Discontinuation for adverse event000 Serious adverse event001 RBV dose reduction2 (20%)5 (20%)3 (12%) Headache20%28% Anemia40%32%16% Fatigue40%16%24% Nausea 10%16%20% Dyspnea10%8% Vomiting04%12% Dizziness08%14% Pruritic rash08%0 Myalgia008% Hyperbilirubinemia grade 304%0 NIH SPARE Oisinusi A. JAMA 2013;310:804-11 Adverse events and laboratory abnormalities, n (%)

7 NIH SPARE Study: SOF + RBV in genotype 1 with advanced liver disease  Summary –In a population of patients with chronic HCV infection with genotype 1 with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of SOF + weight-based or low-dose RBV resulted in SVR 24 rates of 68% and 48%, respectively –The viral kinetics-pharmacodynamics model demonstrated a significantly slower loss rate of infectious virus in participants who subsequently relapsed. the mechanism of incomplete clearance of HCV and relapse in these participants remains elusive –Limitations relatively small sample size higher, though small, increase in the number of discontinuations with low-dose RBV NIH SPARE Oisinusi A. JAMA 2013;310:804-11

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ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

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