in genotypes 1 or 3 with or without cirrhosis gt 18 years Chronic HCV infection Genotype 1 or 3 HCV RNA gt 10 000 IU ml Treatmentnaïve Cirrhosis assessed by liver biopsy or noninvasive tests ID: 620016
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Slide1
C-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosis
> 18 yearsChronic HCV infectionGenotype 1 or 3HCV RNA > 10 000 IU/mlTreatment-naïve Cirrhosis assessed by liver biopsy or noninvasive testsNo HBV or HIV co-infection
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
GZR/EBR + SOF
W4
W6
W8
W12
Randomisation
1
: 1
Open-label
Cirrhosis
No randomisation
Open-label
Cirrhosis
No cirrhosis
No cirrhosis
N = 15
N = 31
N = 30
N = 20
N = 21
N = 12
N = 14
EBR/GZR 50/100 mg
QD ; SOF 400 mg QD
If failure in GT1: retreatment 12 weeks with
EBR/GZR + SOF + RBV 800-1400 mg/day
Objective
SVR
12
(HCV RNA < 15 IU
/ml)
, with 2-sided 95% CI, by
ITT
Lawitz
E. Hepatology 2017;65:439-50
Genotype 1 *
Genotype 3
Design
C-SWIFT
*
Randomisation
stratified
on genotype (1a vs non-1a)Slide2
Genotype 1
Genotype 3
Genotype 1
No cirrhosis
Cirrhosis
No cirrhosis
Cirrhosis
Retreatment
4W
N = 31
6W
N = 30
6W
N = 20
8W
N = 21
8W
N = 15
12W
N = 14
12W
N = 12
12W
N = 25
Mean age, years
52
51
56
57
51
42
55
54
Female, %
35
37
35
38
27
43
17
12
Race, white, %
97
93
100%
95
100
100
100
100
IL28B CC, %
35
27
30
24
40215020Genotype, %1a1b8416871380207624---8812HCV RNA x 106 IU/ml, mean3.693.091.662.373.292.572.266.19Discontinued, N10020012Retreated *, N17341---76% F220% F4
C-SWIFT
Baseline characteristics, and disposition
C-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosis
Lawitz E. Hepatology 2017;65:439-50
* Days from virologic failure to retreatment = 214 (range: 182-260) Slide3
SVR
12 (HCV RNA < 15 IU/ml), mITT
, Genotype 1
3286.780
814 weeks020106 weeks040
06 weeks04008 weeks0211
BreakthroughRelapseNon virologic failureReinfection313020
21
0
20
40
60
80
100
%
Non-cirrhotic
Cirrhotic
92
12 weeks (+ RBV)
0
02 (LTFU)0
25 Relapse
C-SWIFT
C-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosisLawitz
E. Hepatology 2017;65:439-50 Slide4
SVR
12 (HCV RNA < 15 IU/ml), ITT, Genotype 1 with ≥ 6 weeks of treatment, by subg
roups
83.1
87
80.5
100
76.90204060
80100All patientsNoYes
Female
CC
Non-CC
71
30
41
19
52
IL28B genotype
92.5
71 <
2 MIU/ml
> 2 MIU/ml40
31Baseline HCV RNA
75.6
96.2
Male
45
26
Gender%
Genotype
Cirrhosis
1b
84.5
76.9
1a
58
13
Baseline
NS5A
No
Yes
90.2
57.1
61
7
C-SWIFT
C-SWIFT Study: elbasvir/grazoprevir + SOF
in genotypes 1 or 3, with or without cirrhosis
Lawitz
E. Hepatology 2017;65:439-50 Slide5
C-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosis
Impact of RAVs on SVR12 in genotype 1NS3Prevalence at baseline = 66%No impact on SVR12: 76% if no baseline NS3 RAVs vs 69% if presentNS5APrevalence at baseline in the 6- and 8-week groups = 10%SVR12: 90% if no baseline RAVs vs 57% if presentRetreatment group (next generation sequencing analysis, 1% sensitivity threshold)Baseline NS5A RAVs = 14/23 (61%)Baseline NS3 RAVs = 17/23 (74%)
NS3 + NS5A RAVs = 11/23 (48%)SVR12 = 23/23 (2 lost to follow-up)C-SWIFTLawitz E. Hepatology 2017;65:439-50 Slide6
SVR
12 (HCV RNA < 15 IU/ml), mITT
, Genotype 3
Non-cirrhotic Cirrhotic
93
100
83.3
020406080
1008 weeks01012 weeks000
12 weeks011
BreakthroughRelapseEarly discontinuation
15
14
12
%
C-SWIFT
C-SWIFT Study: elbasvir/grazoprevir + SOF
in genotypes 1 or 3, with or without cirrhosisLawitz E. Hepatology 2017;65:439-50 Slide7
SVR
12 (HCV RNA < 15 IU/ml), ITT, Genotype 3, by
subgroups
92.7
100
78.6
96.6
83
89.710086.7
96.2
0
20
4060
80
100
All patients
< 2 MIU/ml
> 2 MIU/ml
No cirrhosisCirrhosis
MaleFemale
CCNon-CC
4127
14
291229
12
15
26Baseline HCV RNA
GenderIL28B genotype
%
C-SWIFT
C-SWIFT Study: elbasvir/grazoprevir + SOF
in genotypes 1 or 3, with or without cirrhosis
Lawitz E. Hepatology 2017;65:439-50 Slide8
NS3 RAV
NS5A RAV
NS5B RAV
Genotype 1 (29 relapses)
56
No resistance-associated variants
28/29 (97%)
18/30 (60%)
30/30 (100%)
Pre-existing baseline RAVs only
0
1 (3%)
0
RAVS detected at failure
1 (3%)
9 (30%)
4/9 in 4W arm
0
RAVs at failure in addition of baseline RAVs
0
2 (7%)
0
Genotype 3 (2 relapses)
At baseline
Q168Q/R
0
0
At relapse
Q168R
Y93H
0
Resistance analysis at failure
C-SWIFT
C-SWIFT Study: elbasvir/grazoprevir + SOF
in genotypes 1 or 3, with or without cirrhosis
Lawitz
E. Hepatology 2017;65:439-50 Slide9
All patients
Genotype 1
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
1 (1)
0
1 (2) *
0
0
Death
0
0
0
0
0
Most common AEs
Headache
Fatigue
Nausea
5 (5)
2 (2)
3 (3)
1 (2)
1 (2)
0
2 (5)
0
1 (2)
1 (3)
0
1 (3)
1 (8)
1 (8)
1 (8)
Hemoglobin
< 10 g
/
dl
1 (1)1 (2)000Total bilirubin > 5 x baseline00000ALT/AST > 5 x ULN00000Adverse events, N (%)* Pneumonia on day 40 of treatment, which led to discontinuation of therapyC-SWIFTC-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosisLawitz E. Hepatology 2017;65:439-50 Slide10
C-SWIFT Study: elbasvir/grazoprevir + SOF in genotypes 1 or 3, with or without cirrhosis
SummaryElbasvir/grazoprevir + sofosbuvir was able to shorten treatment duration to 8 weeks or less among cirrhotic and non-cirrhotic HCV genotype 1 infected patientsGenotype 3 patients achieved high SVR12 rates with 8-12 weeks of therapy, including patients with cirrhosisAll virologic failures were due to relapsePatients relapsed most commonly with either wild-type virus or with RAVs already present at baselineGZR/EBR + SOF was generally safe and well toleratedRetreatment of the patients who failed short-duration therapy was successfully achieved through extended treatment duration
(12 weeks) and the addition of ribavirinC-SWIFTLawitz E. Hepatology 2017;65:439-50