ATTAIN SMV TVR placebo PEGIFN RBV TVR SMV placebo PEGIFN RBV Randomisation 1 1 Doubleblind 18 years HCV genotype 1 HCV RNA 10000 IU ml Null or partial responders to ID: 168524
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Slide1
Reddy KR. Lancet Infect Dis. 2015;15:27-35
ATTAIN
SMV + TVR placebo
+ PEG-IFN + RBV
TVR + SMV placebo + PEG-IFN + RBV
Randomisation*
1 : 1
Double-blind
≥ 18 years
HCV genotype 1HCV RNA ≥ 10,000 IU/mlNull or partial responders to previous PEG-IFN + RBVCompensated cirrhosis allowedNo HBV or HIV co-infection
ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1
Design
N = 384
N = 379
W12
W48
* Randomisation was stratified on genotype (1a or 1b) and previous response to PEG-IFN + RBV (partial or null)
PEG-IFN + RBV
PEG-IFN + RBV
Treatment regimens
SMV : 150 mg
qd
, or placebo ; TVR : 750 mg
tid
, 7-9h apart, or placebo
PEG-IFN
a
-2a : 180
m
g SC once weekly
RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)
Primary efficacy endpoint
Non inferiority of SMV : SVR
12
(HCV RNA < 25 IU
/ml)
by intention to treat (lower margin of the 2-sided 95% CI for the difference with TVR = 12%)Slide2
SMV
N = 379
TVR
N = 384
Median
age, years
50
52
Female
36%
42%
Genotype
1a (Q80K present /Q80K absent)
1b
Other
43% (23% / 77%)
57%
< 1%
42% (17% / 83%)
57%
1%
IL28B CC genotype
4%
5%
HCV RNA log10 IU/ml, median6.566.57Metavir fibrosis score F0-F2 / F3-F456% / 44%55% / 45%Prior treatment with PEG-IFN + RBVNull response62%62%Partial response38%38%Discontinued treatment, nAdverse eventLost to follow-upWithdrawal 2101011294619
Baseline characteristics and patient disposition
Reddy KR. Lancet Infect Dis. 2015;15:27-35
ATTAIN
ATTAIN Study:
simeprevir
versus
telaprevir
,
with PEG-IFN + RBV in previous non responders
with genotype 1Slide3
SVR
12
(HCV RNA < 25 IU
/ml)
difference : - 1.1%
(95% CI : -7.8 to 5.5)
SMV
TVR
On treatment
failure
34%
20%
Viral breaktrough
22%
20%
Relapse
17%
17%
Reddy KR. Lancet Infect Dis. 2015;15:27-35
ATTAIN
ATTAIN Study: simeprevir versus telaprevir,
with PEG-IFN + RBV in previous non responders
with genotype 1
%
SMVTVRN37914538423422014613337272152205444704427643455466840266739020406080100AllPrevious null responsePrevious
partial
response1a
Q80K-
1a Q80K+
1b
Cirrhosis
238
124
215Slide4
NS3 Sequencing
SMV
TVR
Sequencing available
148/176 failures
134/176 failures
Emerging mutations
142/148
111/134
Main mutations detected (positions)
80
122
155
168
36
54
155
156
Reddy KR. Lancet Infect Dis. 2015;15:27-35
ATTAIN
ATTAIN Study: simeprevir versus telaprevir,
with PEG-IFN + RBV in previous non responders
with genotype 1Slide5
SMV, N = 379
TVR, N = 384
AE leading to treatment discontinuation
12 (3%)
39 (10%)
Grade 3 adverse event
72 (19%)
84 (22%)
Grade 4 adverse event
14 (4%)
21 (5%)
Serious adverse event
8 (2%)
33 (9%)
Adverse event of interest
Rash (any type)
81 (21%)
119 (31%)
Pruritus
122 (32%)
170 (44%)
Photosensitivity
8 (2%)
1 (< 1%)
Neutropenia69 (18%)52 (14%)Anemia51 (13%)144 (38%)Dyspnea 27 (7%)36 (9%)Increased bilirubin30 (8%)28 (7%)Additional AE in ≥ 20% of patients in either group
Fatigue
120 (32%)
146 (38%)
Pyrexia
81 (21%)
94 (24%)
Headache
95 (25%)
111 (29%)
Nausea
64 (17%)
109 (28%)
Adverse events, N (%)
Reddy KR. Lancet Infect Dis. 2015;15:27-35
ATTAIN
ATTAIN Study: simeprevir versus telaprevir,
with PEG-IFN + RBV in previous non responders
with genotype 1Slide6
ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders
with genotype 1
SummarySMV + PEG-IFN + RBV showed non-inferiority with regard to SVR
12 to TVR + PEG-IFN + RBV in patients with chronic HCV genotype 1 infection and compensated liver disease who were null or partial responders to previous treatment with PEG-IFN + RBV
Non-inferiority was met for null or partial responders separately as wellRates of on-treatment failure, viral breakthrough, and relapse were similar between the two treatment groupsThe incidence of adverse events deemed at least possibly related
to SMV or TVR was noticeably lower in the SMV group, and most adverse events were grade 1 or 2 Serious adverse events were infrequent and less common in the SMV group, and fewer patients needed to discontinue SMV compared with TVR because of an adverse event
Reddy KR. Lancet Infect Dis. 2015;15:27-35ATTAIN