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BROWSE SLIDES

Design

Baseline characteristics and dosing of medication

• DCV : 60 mg qd
• SOF : 400 mg qd
• RBV (bid dosing) : weight based in genotype 1 : 1000 mg/day if < 75 kg or 1200 mg/day if = 75 kg ; 800 mg/day in genotype 2 or 3 ; dose reduction to 600 mg/day if hemoglobin decreased < 10g/ dL

Baseline characteristics (second cohort) and Objective

• Primary efficacy endpoint : SVR₁₂ (HCV RNA < 25 IU/ml) by mITT analysis
• Secondary endpoints :
  • SVR4
  • SVR₂₄
  • Safety : adverse events, discontinuation for adverse events, grade 3-4 laboratory abnormalities

HCV RNA < 25 IU/ml

• All patients had HCV RNA < 25 IU/ml at end of treatment , except 1 in group B (DCV + SOF 24W)

Virologic relapse post-treatment : 1 patient with genotype 3 who did not received RBV

• NS5A A30K polymorphism (DCV resistance) at baseline and failure

Resistance testing (sequencing)

• NS5A polymorphisms associated with loss of susceptibility to DCV in vitro detected at baseline in 32 patients : 8% in genotype 1, 61% in genotype 2, 28% in genotype 3
• Most frequent mutations : Q30H (genotype 1a), L31M
  (genotype 1b and 2), Y93H (genotype 3)
• Except the patient with relapse, all other patients with preexisting DCV resistant variants had a SVR
• No mutation (S282T) to SOF at baseline or in the patient with breakthrough

Adverse events , n (%)

• Most common : fatigue, headache, nausea (= 25% in any group)
• Grade 3-4 adverse events : 7 (3.3%)
• Discontinuation of treatment for adverse events : 2 (both achieved SVR)
  • DCV-SOF 24W : 1 cerebrovascular accident
  • DCV-SOF + RBV 24W : 1 fibromyalgia exacerbation
• Serious adverse events : 10 (4.7%)
• Most common grade 3-4 laboratory abnormalities : low phosphorus and elevation of glucose levels
• Hemoglobin level more reduced in groups with RBV
  • Reduction of RBV dose in 5 patients because of anemia

Summary

• DCV + SOF was assessed in untreated patients and patients in whom previous treatment with telaprevir or boceprevir had failed
• Most patients had a SVR,
  • including 98% of patients with genotype 1 infection, regardless of viral subtype or failure of prior treatment with PI,
  • and 91% of naïve patients infected with genotype 2 or 3
• The most common adverse event was fatigue, which was reported in approximately one third of patients
• Virologic breakthrough and relapse were rare and were not observed in any of the patients infected with HCV genotype 1 or 2, despite preexisting DCV-resistant variants in 14%
• In genotype 3, 1 relapse in a patient with baseline DCV-resistant variant
• No additional benefit of RBV addition but greater decrease in hemoglobin