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Design

* Recommended dose for immunosuppressive therapy: tacrolimus : 0.5 mg once weekly or 0.2 mg every 3 days, cyclosporine: one-fifth of the daily pre-study dose qd ; dosing subsequently guided by TDM

Treatment regimens

• Co-formulated ombitasvir (OBV)/ paritaprevir (PTV)/ rironavir (r): 25/150/100 mg qd = 2 tablets
• Dasabuvir (DSV): 250 mg bid
• RBV: dose selected by investigator (most often 600-800 mg/day)

Objective

• SVR₁₂ (HCV RNA < 25 IU/ml), with 95% CI, by ITT, descriptive analysis

Baseline characteristics

* At relapse : resistance-associated variants R155K in NS3, M28T and Q30R in NS5A, and G554S in NS5B

• 1 breakthough at W8 : white, hispanic male, GT1a, ILB28 TT ; no pre- or post-transplant HCV treatment, HCV RNA : 5.7 log₁₀ c/ml
• RAV at baseline
  • NS5A : Q30R
• RAV at failure
  • NS5A : Q30R
  • NS3 : Y56H + D168A
  • NS5B : C451R + G558R

Adverse events

Dose modifications for RBV

• In the OBV/PTV/r + DSV + RBV treatment arm, initial total daily doses of RBV ranged from 600–1200 mg, with 48% (13/27) of patients receiving 600 or 800 mg daily at study initiation
• At completion of treatment
  • 41% (11/27) of patients received 600 or 800 mg
  • 33 % (9/27) received 200 or 400 mg
  • and 26% (7/27) received 1000 or 1200 mg daily
• The RBV dose was adjusted
  • for 12 (44%) patients due to adverse events
  • for 10 (37%) patients due to decreases in hemoglobin levels

Summary

• In cohort 2 of the CORAL-I study, adult liver transplant recipients with recurrent HCV genotype 1 and mild to advanced fibrosis achieved high SVR₁₂ rates with the regimen of OBV/PTV/r + DSV ± RBV
• Treatment was generally well tolerated and immunosuppresive drugs (calcineurin inhibitors) dosing was manageable over the period of the study
• The RBV-free regimen of OBV/PTV/r + DSV achieved 100% SVR₁₂ in patients with GT1b infection and will be implemented in future cohort