LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

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Presentation transcript:

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 HCV-trial.com LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Design Randomisation 1 : 1 Open-label W12 N = 25 LDV/SOF SVR12 Genotype 3, naive > 18 years Chronic HCV infection Genotype 3 or 6 Treatment-naive or -experienced HCV RNA ≥ 10 000 IU/ml Compensated cirrhosis allowed * HIV and HBV co-infection excluded LDV/SOF + RBV SVR12 No randomisation Open-label N = 26 Genotype 3, Pre-treated N = 50 LDV/SOF + RBV SVR12 Genotype 6 N = 25 LDV/SOF SVR12 * Biopsy or Fibroscan > 12.5 kPa or Fibrotest > 0.75 and APRI > 2 LDV/SOF: 90/400 mg 1 pill qd ; RBV 1000 or 1200 mg/d in 2 doses, according to body weight Objective SVR12 (HCV RNA < 15 IU/ml), with 2-sided 95% CI, by ITT. No inferential statistics or statistical comparisons were planned. LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 1

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Baseline characteristics Genotype 3 Genotype 6 LDV/SOF Naive N = 25 LDV/SOF + RBV N = 26 Experienced N = 50 Mean age, years 43 48 52 51 Female, % 58 22 36 White, % 88 89 80 16 Genotype: 3 / 3a / 3k / 6 / 6a or 6b, % 4 / 96 / 0 / - / - 0 / 96 / 4 / - / - 6 / 94 / 0 / - / - - / - / - / 68 / 32 Mean HCV RNA, log10 IU/ml 6.3 6.7 Cirrhosis, % 23 44 8 HCV treatment naive 100 92 IL28B CC, % Treatment discontinuation, N Adverse event Lost to follow-up Non adherence to study Consent withdrawal Pregnancy 2 1 - LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 2

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Treatment response Genotype 3 Genotype 6 LDV/SOF naive N = 25 LDV/SOF + RBV N = 26 Experienced N = 50 SVR12 (95% CI) 64 (43-82) 100 (87-100) 82 (69-91) 96 (80-100) Virologic breakthrough, N Relapse, N Discontinuation due to AE, N 8 1 Virologic failure in genotype 3, N = 17 Genotype 3a, N = 16/17 Cirrhosis, N = 9/17 Deep sequencing of NS5A at failure, N = 17 No Y93H, No RAVs associated with NS5A resistance Deep sequencing of NS5B at failure, N = 18 S282T at relapse, N = 2, L159F, N = 1 LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 3

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Treatment-emergent adverse events, N (%) Genotype 3 Genotype 6 LDV/SOF naive N = 25 LDV/SOF + RBV N = 26 Experienced N = 50 Serious adverse event 4 (16%) * 1 (2%) 1 (4%) AE leading to discontinuation of LDV/SOF 1 (4%) ** AE in ≥ 10% of patients, N Headache Upper respiratory tract infection Fatigue Nausea Insomnia Rash Diarrhea Constipation Gastroenteritis Anxiety Cough Hemolytic anemia Vomiting 10 9 5 3 1 2 8 9 2 4 3 1 0 2 3 1 0 4 1 13 9 13 5 10 7 4 1 2 1 2 1 1 2 6 6 0 0 2 4 1 0 0 0 0 0 * 2 related to treatment (upper abdominal pain, abdominal pain) ** diverticular perforation (not related to treatment) LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 4

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Laboratory abnormalities, N (%) Genotype 3 Genotype 6 LDV/SOF naive N = 25 LDV/SOF + RBV N = 26 Experienced N = 50 Hemoglobin, 7.0 to < 9.0 g/dl 5 (19%) 3 (6%) Total bilirubin, > 2.5 to 5.0 ULN 2 (8%) ALT, > 5.0 to 10.0 x ULN 1 (2%) 1 (4%) AST, > 5.0 to 10.0 x ULN Lipase, > 3.0 to 5.0 x ULN Lymphocytes, 350 to < 500/mm3 Neutrophils, 500 to < 750/mm3 LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 5

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2 Summary In this open-label, phase 2 study, all 26 (100%) treatment-naive patients with genotype 3 HCV who were randomized to receive 12 weeks of LDV/SOF + RBV achieved SVR12 as compared with only 16 of 25 (64%) patients who received 12 weeks of LDV/SOF alone The SVR12 rate was 82% in genotype 3 treatment-experienced patients receiving 12 weeks of LDV/SOF + RBV The SVR12 rate was 96% in genotype 6 patients receiving 12 weeks of LDV/SOF At virologic failure No emergence of NS5A RAVs Emergence of S282T in 2 patients and L159F in 1 Most common adverse events were headache, upper respiratory infection, and fatigue Limitation Small size of treatment arms Lack of control group LDV/SOF G3-G6 Gane EJ, Gastroenterology 2015;149:1454-61 6