C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
Randomisation
1:1
Open-label
 Design
N = 31
No cirrhosis
> 18 years
Chronic HCV infection
Genotype 1 or 3
Treatment-naïve
Cirrhosis assessed by liver
biopsy or noninvasive tests
No HBV or HIV co-infection
N = 30
Genotype 1
Cirrhosis
N = 20
N = 21
No cirrhosis
Genotype 3
Cirrhosis
N = 15
N = 14
N = 12
GZR/EBR 100/50 mg QD ; SOF 400 mg QD
W4
W6
W8
W12
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
No randomisation
Open-label
SVR12
 Objective
– SVR12 (HCV RNA < 15 IU/ml), with 95% CI, by ITT
C-SWIFT
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
Baseline characteristics
Genotype 1
No cirrhosis
Genotype 3
Cirrhosis
No cirrhosis
Cirrhosis
4 weeks
N = 31
6 weeks
N = 30
6 weeks
N = 20
8 weeks
N = 21
8 weeks
N = 15
12 weeks
N = 14
12 weeks
N = 12
52
51
56
57
51
42
55
Female
35%
37%
35%
38%
27%
43%
17%
Race, white
97%
93%
100%
100%
95%
100%
100%
IL28B CC
36%
27%
30%
24%
40%
21%
50%
Genotype
1a
1b
84%
16%
87%
13%
80%
20%
76%
24%
-
-
-
0
0
20 (100)
21 (100)
0
0
12 (100)
3.69
3.09
1.66
2.37
3.29
2.57
2.26
Mean age, years
Cirrhosis, N (%)
HCV RNA x 106 IU/ml,
mean
C-SWIFT
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
SVR12 (HCV RNA < 15 IU/ml), mITT, Genotype 1
Non-cirrhotic
Cirrhotic
%
100
87
80
94
80
60
40
33
20
0
Breakthrough
Relapse
Non virologic failure
30
30
20
20
4 weeks
0
20
1
6 weeks
0
4
0
6 weeks
0
4
0
8 weeks
0
1
3
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
SVR12 (HCV RNA < 15 IU/ml), mITT, Genotype 3
%
100
93
Non-cirrhotic
100
Cirrhotic
91
80
60
40
20
0
Breakthrough
Relapse
Early discontinuation
C-SWIFT
15
14
11
8 weeks
0
1
0
12 weeks
0
0
0
12 weeks
0
1
1
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
SVR12 (HCV RNA < 15 IU/ml), per-protocol, Genotype 3, by subgroups
%
100
95
100
97
85
91
100
93
96
28
12
14
26
Male
Female
CC
Non-CC
93
80
60
40
20
0
40
All patients
27
<2M
IU/ml
13
>2M
IU/ml
29
No cirrhosis Cirrhosis
Baseline HCV RNA
C-SWIFT
11
Gender
IL28B genotype
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
Resistance analysis at failure
NS3 RAV
NS5A RAV
Genotype 1 (29 relapses)
NS5B RAV
56
28/29
(97%)
18/30 (60%)
30/30
(100%)
0
1 (3%)
0
1 (3%)
9 (30%)
4/9 in 4W arm
0
0
2 (7%)
0
At baseline
Q168Q/R
0
0
At relapse
Q168R
Y93H
0
No resistance-associated variants
Pre-existing baseline RAVs only
RAVS detected at failure
RAVs at failure in addition of baseline RAVs
Genotype 3 (2 relapses)
C-SWIFT
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
Adverse events, N (%)
Genotype 1
All
patients
Genotype 3
Non cirrhotic
4 & 6 weeks
N = 61
Cirrhotic
6 & 8 weeks
N = 41
Non cirrhotic
8 & 12 weeks
N = 29
Cirrhotic
12 weeks
N = 12
Discontinuation due to AE
1 (1)
0
1 (2)
0
0
Serious adverse event
2 (2)
0
2 (5)
0
0
0
0
0
0
0
4 (4)
1 (2)
2 (7)
1 (3)
1 (8)
2 (2)
2 (2)
2 (3)
2 (3)
0
0
1 (8)
1 (2)
1 (3)
1 (8)
0
0
0
Death
Most common AEs
Headache
Fatigue
Nausea
Hemoglobin < 10 g/dl
0
Total bilirubin > 5 x baseline
0
0
0
0
0
ALT/AST > 5 x ULN
0
0
0
0
0
C-SWIFT
Poordad F. EASL 2015, Abs. O006
C-SWIFT Study: grazoprevir/elbasvir + SOF
in genotypes 1 or 3, with or without cirrhosis
 Summary
– Grazoprevir/elbasvir + sofosbuvir was able to shorten treatment
duration to 8 weeks or less among cirrhotic and non-cirrhotic HCV
genotype 1 infected patients
– Genotype 3 patients achieved high SVR12 rates with 8-12 weeks
of therapy, including patients with cirrhosis
– All virologic failures were due to relapse
– Patients relapsed most commonly with either wild-type virus or
with RAVs already present at baseline
– GZR/EBR + SOF was generally safe and well tolerated
C-SWIFT
Poordad F. EASL 2015, Abs. O006