Design Objective SVR 12 HCV RNA lt 25 IUml in genotype 1 DCV 60 mg qd SOF 400 mg qd RBV DCV 60 mg qd SOF 400 mg qd RBV Not randomised Openlabel ALLY1 Study DCV SOF RBV for advanced liver disease and postliver transplant recurrence ID: 617278
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Slide1
ALLY-1
Design
Objective
SVR
12
(HCV RNA < 25 IU/ml) in genotype 1
DCV 60 mg
qd
+ SOF 400 mg qd + RBV
DCV 60 mg qd + SOF 400 mg qd + RBV
Not randomisedOpen-label
ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence
W12
N = 53
≥ 18 years
Chronic HCV infectionAll genotypesTreatment-naïve or experiencedNS5A inhibitor-naïveAdvanced cirrhosis* or post-liver transplant recurrence**
Poordad F. Hepatology 2016, Jan 11 (Epub ahead of print)
Post-transplant recurrence
SVR12
SVR12
N = 60
Advanced cirrhosis
* Child-Pugh A, B or C, MELD score 8-40, hepatocarcinoma allowed** ≥ 3 months post-transplant, no rejection, any immunosuppressive regimen
RBV : 600 mg/day (bid dosing), adjusted to 1000 mg/day,
based on hemoglobin and
creatinine
clearance Slide2
Advanced cirrhosis
N = 60
Post-transplant
N = 53
Median age, years
58
59
Female
37%
28%
HCV RNA log
10
IU/ml, mean
6.01
6.61
IL28B CC genotype
22%
25%
Genotype
1a
1b
2
3
4
657%18%8%10%7%058%19%021%02%Fibrosis stage by Fibrotest : F0-F2 / F3 / F4-43% / 35% / 30%
Baseline characteristics
Advanced cirrhosis cohort Child Pugh A = 12 (MELD score 10-15 : 5/12) B = 32 (2/3 with ascites and/or encephalopathy, MELD score 10-20 : 25/32) C = 16 (all with ascites and encephalopathy ; MELD score ≥ 16 : 13/16)
ALLY-1
ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence
Poordad
F.
Hepatology
2016, Jan 11 (
Epub
ahead of print)Slide3
SVR
12
(
HCV RNA < 25 IU/ml)
Advanced fibrosis
Post-transplant
%
25
5010075
82
9583
94
92
94
56
91
76
76
78
96
N
45
41
60
12321623372337HepaticencephalopathyABYesCNoAlbuming/dlYes≥ 2.8Genotype 1AllNoChild-PughAscites5395
5642
18< 2.8
GT 1a
Other
g
enotypes
26
22
34
31
97
92
91
ALLY-1
ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence
Poordad
F.
Hepatology
2016, Jan 11 (
Epub
ahead of print)Slide4
NS5A variants (-28, -30, -31, or -93 polymorphisms) detected in 22 of 112 patients
82% (18/22) achieved SVR
12
10/14 in cirrhosis cohort ; 8/8 in post-transplant cohort
90% (81/90) without NS5A polymorphisms achieved
SVR
1239/45 in cirrhosis cohort ; 42/45 in post-transplant cohort
No NS5B-S282 variants detected at baseline or failure
Advanced cirrhosisPost-transplantVirologic failures, N10 (9 relapses)
3 (all relapses)NS5A RAVs at baseline, n/N*4/100/3
NS5A RAVs at failure, n/N*
10/10
3/3
* Assessed by population-based
sequencing
ALLY-1ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrenceNS5A resistance-associated variants in patients with
virologic failureBaseline resistance polymorphismsPoordad F. Hepatology
2016, Jan 11 (Epub
ahead of print)Slide5
Advanced
c
irrhosis
N = 60
Post-transplant
N = 53
Death
0
0Serious adverse event
10 (17%), all unrelated5 (9%), all unrelatedGrade 3 or 4 adverse event*
11 (18%)
4 (8%)
Discontinuations
due to adverse event
All study medications
1 (2%)
1 (2%)
RBV only
10 (17%)
4 (8%)
AE (any grade)
in ≥ 10%
in either cohortHeadache9 (15%)19 (36%)Fatigue11 (18%)15 (28%)Anemia12 (20%)10 (19%)Diarrhea5 (8%)10 (19%)
Nausea
10 (17%)3 (6%
)
Arthralgia
1 (2%)
7 (13%)
*
4 events (anemia, non-cardiac chest pain, arthralgia, headache) considered related to study
medication
Adverse events, n (%)
ALLY-1
ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence
Poordad
F.
Hepatology
2016, Jan 11 (
Epub
ahead of print)Slide6
SummarySVR12
achieved by 94% of liver transplant recipients with HCV recurrenceFavorable drug-drug interaction profile that did not require dose modification of pre-transplant or immunosuppressant medications
No events of graft rejection
SVR12 in 92% of patients with Child-Pugh class A cirrhosis, 94% in class B, 56% in class CHigh SVR12 rates in GT-3 patients: 83% of advanced
cirrhosis, 91% of post-transplantSVR12 rate of only 76% in genotype 1 advanced cirrhosis
ALLY-1
ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence
Poordad F.
Hepatology 2016, Jan 11 (Epub ahead of print)