12 HCV RNA lt 25 IUml with 95 CI DCV 60 mg qd SOF 400 mg qd DCV 60 mg qd SOF 400 mg qd Not randomised Open label ALLY3 Study DCV SOF for HCV genotype 3 W12 ID: 639729
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Slide1
ALLY-3
Design
Objective
SVR
12
(HCV RNA < 25 IU/ml),
with
95% CI
DCV 60 mg qd + SOF 400 mg qd
DCV 60 mg qd + SOF 400 mg qd
Not randomisedOpen-label
ALLY-3 Study: DCV + SOF for HCV genotype 3
W12
N =
51
≥ 18 yearsChronic HCV infectionGenotype 3Treatment-naïve or experiencedNS5A inhibitor-naïveHCV RNA ≥ 50,000 IU/mlCirrhosis* allowedNo HBV or HIV co-infection
Nelson DR. Hepatology 2015;61:1127-35
Treatment-experienced
SVR12
SVR12
N = 101
Treatment-naïve
*
Metavir
F4, or
Fibroscan
> 14.6
kPa
, or
Fibrotest
®
≥ 0.75 + APRI > 2Slide2
Treatment-naïve
N = 101
Treatment-experienced*
N = 51
Median age, years
53
58
Female
43%
37%
White / black
91% / 4%
88% / 4%
HCV RNA ≥ 800,000 IU/ml
69%
75%
IL28B CC genotype
40%
39%
Cirrhosis
19%
25%
Fibrosis stage by
Fibrotest, F422%16%Past treatment categoryRelapseNull responsePartial responseOther failure (intolerance, breakthrough)-61%14%4%22%Discontinuation1 (pregnancy)0
Baseline characteristics and patient disposition
* 7 patients with previous failure to SOF, and 2 to alisporivir
ALLY-3 Study: DCV + SOF for HCV genotype 3
ALLY-3
Nelson DR.
Hepatology
2015;61:1127-35Slide3
SVR
12
(
HCV RNA < 25 IU/ml)
Treatment-naïve
Treatment-experienced
By sub-groups
SVR
12 in 5/7 prior failure to SOF and in 2/2 prior failure to alisporivir ALLY-3 Study: DCV + SOF for HCV genotype 3
ALLY-3Nelson DR. Hepatology 2015;61:1127-35
25
50
100
75
90*
95%
73
86**
All
91
63
86
94
907092879188N101762251438906214210441086092F0-F3F4BaselineHCV RNA, IU/mlMF< 800K< 65≥ 65IL28BCCNon-CC* 95% CI:83-95
**95% CI:74-94
Fibrotest
Fibrotest
All
F0-F3
F4
≥ 800K
Gender
Age, years
0Slide4
Virologic
failure
ALLY-3 Study: DCV + SOF for HCV genotype 3
Virologic breaktrough : none
Failure at end of treatment : 1 naïve patient with cirrhosis Post-treatment relapse 9 in the naïve group (cirrhosis : 7/9) 7 in the pre-treated group (cirrhosis : 4/7) 15/16 occurred by W4 post-treatment
Emergence of resistance-associated variant : 10/16 Y93H, n = 9 L31I, n = 1 In the 6 other : presence of baseline Y93H variant No NS5B-resistant variants (159, 282, 321) detected at baseline or relapse
ALLY-3
Nelson DR.
Hepatology 2015;61:1127-35Slide5
Adverse events and Grade 3-4 laboratory abnormalities, N (%)
N = 152
Adverse event leading to discontinuation
0
Serious AE (gastrointestinal hemorrhage, not related)
1
Grade 3 AE (arthralgia, food poisoning, GI hemorrage)
3 (2%)
AE in ≥ 5 % of patients
Headache
20%
Fatigue
19%
Nausea
12%
Diarrhea
9%
Insomnia
6%
Abdominal pain
5%
Arthralgia
5%
Lymphocytes < 500/ml1 (1%)Platelets < 50 x 109/l2 (1%)INR > 2 x ULN2 (1%)ALT or AST > 5 x ULN or total bilirubin > 2.5 x ULN0Lipase > 3 x ULN
3 (2%)
ALLY-3
Study
: DCV + SOF for HCV genotype 3
ALLY-3
Nelson DR.
Hepatology
2015;61:1127-35Slide6
ALLY-3 Study: DCV + SOF for HCV genotype 3
SummaryA 12-week regimen of DCV plus SOF achieved SVR12 in 96% of treatment-naïve and treatment-experienced patients with genotype 3 infection without cirrhosis and was well tolerated
SVR in patients with cirrhosis was sub-optimal
SVR12 rates were comparable across subgroups based on gender, age, baseline HCV-RNA levels, and IL28B genotypeAmong the 16 patients with relapse, 11 had cirrhosis 6/13 patients with baseline Y93H variant had relapse post-treatment, including 3 of 4 patients with cirrhosisSafety was good with no discontinuation for adverse event
ALLY-3
Nelson DR.
Hepatology
2015;61:1127-35