 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV + RBV No randomisation Open-label CORAL-I Study cohort.

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Presentation transcript:

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV + RBV No randomisation Open-label CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence W years Recurrent HCV infection, genotype 1, post-liver transplantation for HCV ≥ 12 months ago Mild and advanced fibrosis (≤ F3) Naïve or pre-treated with IFN or PEG-IFN + RBV Stable calcineurin inhibitor ≥ 2 months * Mantry PS. AASLD 2015, Abs SVR 12  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 mg/day) OBV/PTV/r + DSV GT1a ; GT1b non-responders to prior IFN or PEG-IFN + RBV GT1b Naïve or Relapsers SVR 12 * 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 N = 27 N = 13  Design CORAL-I, cohort 2

CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence OBV/PTV/r + DSV + RBV N = 27 OBV/PTV/r + DSV N = 13 Mean age, years5862 Female15%38% White / Black96% / 4%100% / 0 Genotype 1a / 1b, N21 / 60 / 13 HCV RNA, log 10 IU/ml, mean 6.7 ± 0.77 ± 0.4 Fibrosis stage : F0-F1/ F2 / F3, N16 / 9 / 18 / 2 / 3 IL28B CC genotype15%69% Post-liver transplant retreatment (IFN or PEG-IFN ± RBV : naïve / non-response / relapse, N 15 / 12 / 08 / 0 / 5 Time since liver transplantation, median months6399 Primary immunosuppressive regimen Tacrolimus78%38% Cyclosporine22%62% Baseline characteristics Mantry PS. AASLD 2015, Abs CORAL-I, cohort 2

Mantry PS. AASLD 2015, Abs CORAL-I, cohort 2 CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence  1 breakthough at W8 : white, hispanic male, GT1a, ILB28 TT ; no pre- or post-transplant HCV treatment, HCV RNA : 5.7 log 10 c/ml  RAV at baseline –NS5A : Q30R  RAV at failure –NS5A : Q30R –NS3 : Y56H + D168A –NS5B : C451R + G558R OBV/PTV/r + DSV OBV/PTV/r + DSV + RBV Overall 98 %

CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence OBV/PTV/r + DSV + RBV N = 27 OBV/PTV/r + DSV N = 13 Serious adverse events10 Discontinuation due to adverse event01 Adverse events in > 15% of all patients Fatigue52%31% Nausea41%15% Rash33%0 Anemia30%0 Headache30%15% Asthenia26%7.7% Diarrhea22%7.7% Cough19%15% Hemoglobin 8-10 g/dl19%0 Total neutrophils Grade 3 ( < 1 000/mm 3 )00 AST grade 3 / ALT grade 30 / 0 Total bilirubin Grade 3 (3-10 x ULN)3.7%0 Adverse events Mantry PS. AASLD 2015, Abs CORAL-I, cohort 2

CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence  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 Mantry PS. AASLD 2015, Abs CORAL-I, cohort 2 Dose modifications for RBV

CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence  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 SVR 12 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% SVR 12 in patients with GT1b infection and will be implemented in future cohort Mantry PS. AASLD 2015, Abs CORAL-I, cohort 2