AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
 Design
No randomization
Arm A :
18-65 years
HCV genotype 4
Egyptian
Naïve or pre-treated
with PEG-IFN + RBV
No cirrhosis (open-label)
or compensated cirrhosis
(randomisation)
No HBV or HIV co-infection
N = 59
No cirrhosis
W12
W24
OPV/PTV/r + RBV
Randomization 1:1
Arm B :
N = 31
compensated cirrhosis
Arm C :
N = 29
compensated cirrhosis
OPV/PTV/r + RBV
OPV/PTV/r + RBV
 Treatment regimens
–
–
Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg qd = 2 tablets
Weight-based RBV (bid dosing)
 Objective
–
AGATE-II
SVR12 (HCV RNA < LLOQ), with 2 sided 95% confidence interval, treatment-emergent
adverse events
Esmat G. AASLD 2015, Abs. 708
AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
Baseline characteristics
No cirrhosis 12W
N = 100
Cirrhosis 12W
N = 31
Cirrhosis 24W
N = 29
49
57
56
Female
30%
6%
24%
Mean BMI, kg/m2
29.1
29.3
31.0
Mean HCV RNA, log10 IU/Ml
6.0
6.0
6.0
68 / 11 / 19 / 2
0 / 0 / 3 / 97
0 / 0 / 0 /100
Treatment-naïve, %
49
48
52
Treatment-experienced, %
Null responder
Partial responder
Relapser
33
8
10
29
6
16
24
7
17
Mean platelet count (x 109/l)
229
156
138
44.7 ± 3.0
41.8 ± 4.4
40.3 ± 5.3
15
29
24
Mean age, years
Fibrosis stage (%) : F0-F1 / F2 / F3 / F4
Mean albumin (g/l)
History of diabetes, %
AGATE-II
Esmat G. AASLD 2015, Abs. 708
AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
SVR rates by treatment arm
100
94
97
97
80
60
40
20
28/29
%
Data Pending – Study in Progress
%
SVR12 by baseline fibrosis stage
(12 week treatment arms)
94/100
30/31
SVR12
SVR12
SVR4 SVR12
Arm A
No-cirrhosis
12 weeks
Arm B
Cirrhosis
12 weeks
Arm C
Cirrhosis
24 weeks
0
AGATE-II
100
95
94
94/99
30/32
< F3
= F4
80
60
40
20
0
Baseline fibrosis stage
Esmat G. AASLD 2015, Abs. 708
AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
Reasons for not achieving SVR12
Non-response
On-treatment virologic failure
Premature study drug discontinuation
Missing SVR12 data
Relapse by W12 post-treatment
No cirrhosis
W12
Cirrhosis
W12
Cirrhosis
W24
2/100 (2.0%)
1/31 (3.2%)
1/29 (3.4%)
1 (1.0%) *
1 (3.2%)
1/29
1 (1.0%)
withdrew consent
0
0
1/100
0
NA**
3/98 (3.1%) *
0
NA**
* Includes 1 patient with compensated cirrhosis miscategorized as non-cirrhotic and assigned in Arm A
** Study ongoing
AGATE-II
Esmat G. AASLD 2015, Abs. 708
AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
Treatment-emergence adverse events
No cirrhosis W12
N = 100
Any treatment-emergent adverse event
72 (72%)
Adverse event leading to discontinuation
0
Serious adverse event, %
2
Severe adverse event, %
2
Death, N
1
Adverse events occurring in ≥ 10% in either group, %
Headache
40
Fatigue
33
Pruritus
23
Dyspepsia
15
Upper abdominal pain
16
ALT ≥ Grade 2 (> 3 x ULN)
0
AST ≥ Grade 2 (> 3 x ULN)
0
Total bilirubin grade 3 (> 3-10 x ULN), %
2
Hemogloblin 8-10 g/dl, N (%)
7 (7)
RBV dose reduction, N
10
AGATE-II
Cirrhosis W12
N = 31
Cirrhosis W24
N = 29
21 (68%)
0
0
0
0
25 (86%)
0
7
7
0
29
23
13
10
6
0
0
6
2 (6)
4
34
38
31
14
10
0
0
14
4 (14)
7
Esmat G. AASLD 2015, Abs. 708
AGATE-II Study: OBV/PTV/r + RBV in genotype 4
Egyptian patients without or with cirrhosis
 Summary
– High SVR rates were achieved in HCV genotype 4-infected
Egyptian patients without cirrhosis or with compensated cirrhosis
after 12 weeks of OBV/PTV/r + RBV weeks: SVR12 was 94%
and 97%, respectively
– 12 weeks treatment was well tolerated with no treatment
discontinuations due to adverse events
– Prolongation of therapy to 24 weeks does not provide additional
benefit, with more serious adverse events and a higher frequency
of hemoglobin decrease
AGATE-II
Esmat G. AASLD 2015, Abs. 708