1. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
ARV-trial.com
C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
Design
Randomisation
1 : 1
Open-label W8
W12
W16
EBR/GZR + SOF + RBV
Naive
≥ 18 years
Chronic HCV infection
Genotype 3
Treatment-naïve or
PEG-IFN experienced
Compensated cirrhosis**
No HBV co-infection
EBR/GZR + SOF
EBR/GZR + SOF
Experienced*
EBR/GZR + SOF + RBV
EBR/GZR + SOF
** Liver biopsy or
Fibroscan > 12.5 kPa
* Randomisation of treatment-experienced patients was stratified
on prior relapse vs non relapse (partial, null, interferon-intolerant)
EBR/GZR 50/100 mg 1 tablet QD ; SOF 400 mg QD ; RBV mg/day
Objective
Primary endpoint: SVR12 (HCV RNA < 15 IU/mL), full analysis set (patients who received ≥ 1 dose of study drug)
C-ISLE
Foster GR. AASLD 2016, Abs. 74 1

2. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
ARV-trial.com
C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
Baseline characteristics
Genotype 3 with cirrhosis
N = 100
Mean age, years
53.4
Female, % 32
Race : white / asian %
69 / 29
Fibroscan® score, mean kPa
HCV RNA log10 IU/mL, mean
6.2
IL28B CC, % 50
Prior treatment history, %
Naive
PEG-IFN experienced 47 53
Platelets x 103/mm3, mean
< 100 x 103/mm3, %
148 24
C-ISLE
Foster GR. AASLD 2016, Abs. 74 2

3. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
SVR12 (FAS), %
Treatment-naive
Treatment-experienced %
100
96*
100 91
94*
94* 75 50 25 n 23 23 17 18 18
EBR/GZR
+ SOF + RBV
(8 weeks)
EBR/GZR
+ SOF
(12 weeks)
EBR/GZR
+ SOF
(12 weeks)
EBR/GZR
+ SOF + RBV
(12 weeks)
EBR/GZR
+ SOF
(16 weeks)
Relapse 2
Non virologic failure 1*
1**
1***
* SVR12 = 100% in mFAS analysis, excluding patients who discontinued treatment for reasons unrelated to study medication (* lost to follow-up, ** consent withdrawal, *** discontinuation at D7 for cellulitis)
C-ISLE
Foster GR. AASLD 2016, Abs. 74

4. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
ARV-trial.com
C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
Resistance data
SVR12 according to baseline NS5A RAVs (15% sensitivity threshold): NS5A polymorphisms at positions 24, 28, 30, 31, 32, 38, 58, 62, 92, or 93)
98% (48/49) if RAVs
98% (46/47) if no RAVs
If Y93H present (N = 4): SVR12 = 0/1 (relapse) if 8 weeks treatment ; 3/3 (100%) if > 8 weeks treatment
2 relapses
Both patients received EBR/GZR/SOF + RBV for 8 weeks
No NS5A RAVS at baseline or failure in 1 patient
In 1 patient : NS5A RAVs at baseline : Y93H, P58, S62T ; at failure : P58 and S62T
C-ISLE
Foster GR. AASLD 2016, Abs. 74 4

5. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
ARV-trial.com
C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
Adverse events
EBR/GZR + SOF + RBV
8 weeks
N = 23
EBR/GZR + SOF
12 weeks
N = 41
N = 18
16 weeks
Drug-related adverse event, %
Fatigue
Nausea
Skin rash/pruritus 13
17.4
8.7
22.0
9.8
7.3
50.0
27.8
44.4
16.7
11.1
Serious adverse event, N (%) *
1 (2.4)
3 (16.7)
1 (5.6)
Discontinuation due to adverse event, N (%)
1 (5.6) **
Laboratory abnormalities, %
Hemoglobin < 10 g/dL
Total bilirubin > 5 x baseline
AST/ALT > 5 x ULN
2.4
* Lung infection, creatinine increased, chest pain, opiate overdose, and cellulitis
** 1 patient discontinued treatment at Day 7 due to cellulitis
C-ISLE
Foster GR. AASLD 2016, Abs. 74 5

6. C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
ARV-trial.com
C-ISLE study: EBR/GZR + SOF + RBV in genotype 3 and cirrhosis
Summary
High efficacy was demonstrated in treatment-naive and treatment-experienced cirrhotic HCV genotype 3-infected patients
There were no virologic failures among patients receiving EBR/GZR + SOF + RBV for 12 or 16 weeks
Treatment duration longer than 12 weeks is not needed
High efficacy was seen regardless of
presence of baseline NS5A RAVs
or patient characteristics
Generally safe and well tolerated
C-ISLE
Foster GR. AASLD 2016, Abs. 74 6