No HBV or HIV co-infection

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Presentation transcript:

No HBV or HIV co-infection C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 Design Randomisation 1 : 1 Open-label W12 W18 > 18 years HCV genotype 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve No cirrhosis No HBV or HIV co-infection N = 21 GZR + EBR + RBV SVR12 GZR + EBR + RBV N = 20 Grazoprevir (GZR) : 100 mg qd Elbasvir (EBR) : 50 mg qd RBV (bid dosing) : 800mg/day if 51-65 kg, 1000 mg/day if 66-80 kg, 1200 mg/day if 81-105 kg, 1400 mg/day if > 105 kg Primary efficacy endpoint SVR12 (HCV RNA < 25 IU/ml), with 2-sided 95% CI, comparison between groups (intention to treat analysis) C-WORTHY/D Gane E. EASL 2015, Abs. P0776

C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 Baseline characteristics and patient disposition GZR + EBR + RBV 12 weeks (N = 20) GZR + EBR + RBV 18 weeks (N = 21) Female 60% 62% Age, years (mean) 49 42 IL28B CC 40% 38% HCV RNA ≤ 10M IU/ml 75% 76.2% Metavir F0-F2 / F3 95% / 5% 95.2% / 4.8 % Discontinuation On-treatment failure Adverse event Lost to follow-up, Withdrew consent 2 1 C-WORTHY/D Gane E. EASL 2015, Abs. P0776

C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 SVR12 (HCV RNA < 25 IU/ml), % (95% CI), ITT % 100 57.1 (34.0-78.2) 75 45.0 (23.1-68.5) 50 25 20 21 12 weeks 18 weeks Rebound 3 2 Breakthrough 6 5 Futility 1 (quantifiable virus at TW8) Relapse C-WORTHY/D Gane E. EASL 2015, Abs. P0776

Resistance associated variants in subjects with virologic failure C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 Resistance associated variants in subjects with virologic failure NS3 RAVs NS5A RAVs 12W arm At baseline At failure Breakthrough V170I WT A30S, Y93Y/H, L31L/I Q80K A30S, Y93H Rebound na V170I, A156G Y93H Q80K, V170I V170I, A156G, Q80K V170I, L132I Q80R, V170I, L132I Futility A30A/E/K/T, Y93H Y56Y/H, Q168Q/K, V170I 18W arm V170I, Q168R L31F A156G A30K A30K, P58S C-WORTHY/D Gane E. EASL 2015, Abs. P0776

SVR12 according to baseline RAVs C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 SVR12 according to baseline RAVs Overall Population GZR + EBR + RBV 12 weeks GZR + EBR + RBV 18 weeks Overall efficacy, n/N (%) 21/38 (55%) 9/19 (47%) 12/19 (63%) NS3 RAVs not detected, n/N (%) 3/3 (100%) 2/2 (100%) 1/1 (100%) NS3 RAVs at baseline, n /N (%) 18/35 (51%) 7/17 (41%) 11/18 (61%) NS5A RAVs not detected, n/N (%) 18/31 (58%) 7/14 (50%) 11/17 (65%) NS5A RAVs at baseline, n/N (%) 3/7 (43%) 2/5 (40%) 1/2 (50%) C-WORTHY/D Gane E. EASL 2015, Abs. P0776

GZR + EBR + RBV 12 weeks (N = 20) GZR + EBR + RBV 18 weeks (N = 21) C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 Adverse events, N (%) GZR + EBR + RBV 12 weeks (N = 20) GZR + EBR + RBV 18 weeks (N = 21) Adverse events Headache Upper respiratory tract infection Accidental overdose Insomnia Rash Nausea Asthenia 17 (85.0) 5 (25.0) 3 (15.0) 2 (10.0) 19 (90.5) 5 (23.8) 2 (9.5) 3 (14.3) Serious adverse event Serious drug-related adverse event Discontinuation due to adverse event 1* (4.8) * dyspnea, fatigue and asthenia 2-3 days after starting treatment C-WORTHY/D Gane E. EASL 2015, Abs. P0776

C-WORTHY Study Part D : grazoprevir + elbasvir + RBV in genotype 3 Summary Efficacy of 12 or 18 weeks of GZR + EBR + RBV in HCV genotype 3 infected patients Was suboptimal due to on-treatment virologic failure in 17 of 41 patients No subject relapsed after the end of therapy NS5A RAVs found in 16 of 17 failures, Y93H the most common NS5A RAV identified GZR + EBR + RBV was generally safe and well tolerated Adverse events were slightly more common in the 18 week arm compared with the 12 week arm No differences in serious adverse events or laboratory abnormalities Adverse event considered to be severe in intensity reported in only 1 patient (non-drug related depression during follow-up) C-WORTHY/D Gane E. EASL 2015, Abs. P0776