Kwo PY. NEJM 2014;371:2375-82CORAL-I

Design

OBV/PTV/r + DSV + RBV

Open labelPhase II

18-70 yearsChronic HCV infection, genotype 1

Liver transplantation for HCV≥ 12 months ago

HCV RNA > 10,000 IU/mlTreatment naïve or prior IFN-based

regimen prior to transplantationMetavir ≤ F2 by biopsy

No HBV or HIV coinfection

CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

W24

N = 34

Stable immunosuppressive therapy : tacrolimus or cyclosporin ; glucocorticoïds at dose ≤ 5 mg/day permitted Treatment regimens

– Co-formulated ombitasvir/paritaprevir/rironavir/ (OBV/PTV/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, by intention to treat, with 95% CI, descriptive analysis

N = 34Demographics and clinical characteristics

Mean age, years 60

Female 31%

Genotype 1a 85%

IL28B CC genotype 24%

HCV RNA log10 IU/ml, mean (SD) 6.6 ± 0.5

Metavir F0 / F1 / F2, % 18% / 38% / 44%

Lack of response to previous IFN treatment 71%

Time since liver transplantation, months, median 39.5

Tacrolimus / ciclosporine, % 85% / 15%

Outcome, % (95% CI)HCV RNA < 25 IU/ml at W24 (end of treatment) 100% (90-100)

SVR12 (HCV RNA < 25 IU/ml) 97% (85-100)

Relapse, n, % 1* , 3%

Baseline characteristics and treatment response

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

Kwo PY. NEJM 2014;371:2375-82CORAL-I

CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

AE leading to discontinuation 1 (3%)*

Serious adverse events 2 (6%)

Fatigue 50%

Headache 44%

Cough 32%

Anemia 29%

Diarrhea 26%

Insomnia 26%

Asthenia 24%

Nausea 24%

Muscle spasms 21%

Back pain 18%

Dizziness 18%

Peripheral edema 18%

Rhinorrhea 18%

Adverse events and laboratory abnormalities in the 34 patients, N (%)

Grade 3 laboratory abnormalitiesALT 0

AST 0

Total bilirubin 2 (6%)

Hemoglobin 1 (3%)

Creatinine 0

* W18 : rash, memory impairment, and anxiety.SVR12 despite premature discontinuation

No graft rejection and no deaths

Kwo PY. NEJM 2014;371:2375-82CORAL-I

CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

Summary– In this phase II trial of a 24-week, IFN-free, all-oral antiviral regimen for

HCV genotype 1 infection, a rate of sustained virologic response of 97% (95% CI, 85 to 100) at post-treatment weeks 12 and 24 was observed among liver-transplant recipients with no fibrosis or mild fibrosis.

– No deaths or episodes of graft rejection– Very good tolerability and safety– No patient needed a blood transfusion ; 5 patients (15%) required

erythropoietin, all of whom had initially received RBV at a total daily dose of 1000 or 1200 mg

• Given the high SVR12, regardless of the initial RBV dose, an initial dose of 600 to 800 mg may provide sufficient therapeutic benefit and minimize the risk of severe anemia

– Limitations• Patients with advanced fibrosis excluded• Patients with aggressive forms of recurrent HCV infection (e.g., fibrosing

cholestatic hepatitis) excluded

Kwo PY. NEJM 2014;371:2375-82CORAL-I