Objective SVR 12 (HCV RNA 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV +...

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

OBV/PTV/r + DSV + RBV

No randomisationOpen-label

CORAL-I Study cohort 2: OBV/PTV/r + DSV + RBV for post-transplant genotype 1 HCV recurrence

W24

18-70 yearsRecurrent 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 + RBVStable calcineurin inhibitor ≥ 2 months *

Mantry PS. AASLD 2015, Abs. 1084

SVR12

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)

OBV/PTV/r + DSV

GT1a ;GT1b non-respondersto prior IFN or PEG-IFN + RBV

GT1bNaïve orRelapsers

SVR12

* 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


OBV/PTV/r + DSV + RBVN = 27

OBV/PTV/r + DSVN = 13

Mean age, years 58 62Female 15% 38%White / Black 96% / 4% 100% / 0Genotype 1a / 1b, N 21 / 6 0 / 13HCV RNA, log10 IU/ml, mean 6.7 ± 0.7 7 ± 0.4Fibrosis stage : F0-F1/ F2 / F3, N 16 / 9 / 1 8 / 2 / 3IL28B CC genotype 15% 69%Post-liver transplant retreatment (IFN or PEG-IFN ± RBV : naïve / non-response / relapse, N 15 / 12 / 0 8 / 0 / 5

Time since liver transplantation, median months 63 99Primary immunosuppressive regimen

Tacrolimus 78% 38%Cyclosporine 22% 62%

Baseline characteristics

Mantry PS. AASLD 2015, Abs. 1084CORAL-I , cohort 2



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

0

40

60

80

100

OBV/PTV/r+ DSV

100

13

20

18 27

96

OBV/PTV/r+ DSV + RBV

Overall

98%


OBV/PTV/r + DSV + RBVN = 27

OBV/PTV/r + DSVN = 13

Serious adverse events 1 0Discontinuation due to adverse event 0 1Adverse events in > 15% of all patients

Fatigue 52% 31%Nausea 41% 15%Rash 33% 0Anemia 30% 0Headache 30% 15%Asthenia 26% 7.7%Diarrhea 22% 7.7%Cough 19% 15%

Hemoglobin 8-10 g/dl 19% 0Total neutrophils Grade 3 ( < 1 000/mm3) 0 0AST grade 3 / ALT grade 3 0 / 0 0 / 0Total bilirubin Grade 3 (3-10 x ULN) 3.7% 0

Adverse events



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


Dose modifications for RBV


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


Objective SVR 12 (HCV RNA 25 IU/ml), with 95% CI, by ITT, descriptive analysis OBV/PTV/r + DSV +...

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