Randomisation 1 1 1870 years HCV genotype 1 Naïve or pretreated with IFNbased regimen No cirrhosis HCV RNA 10000 IU ml No prior therapy with PI No HBV or HIV coinfection OPTIMIST1 Study SMV SOF for genotype 1 ID: 632536
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Slide1
SMV 150 mg QD + SOF 400 mg QD
Randomisation
1 : 1
18-70 years
HCV genotype 1Naïve or pre-treatedwith IFN-based regimenNo cirrhosisHCV RNA ≥ 10.000 IU/mlNo prior therapy with PINo HBV or HIV co-infection
OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
N = 155
N = 155
W12
*
Randomisation was stratified on genotype (1a with Q80K or 1a without Q80K or 1b), IL28B (CC or non-CC) and prior HCV treatment history (naïve/relapse or non-response or other)
ObjectiveSVR12 : superiority of SMV + SOF vs historical control of approved DAA + PEG-IFN + RBV regimens (composite SVR12 of 83% for 8 weeks and 87% for 12 weeks, with a lower limit of the 95% CI > SVR12 of historical control). If superiority, assessment of non-inferiority of 8 vs 12 weeks of SMV + SOF. Analyses by ITT
SMV 150 mg QD
+ SOF 400 mg QD
W8
OPTIMIST-1
Design
Kwo
P.
Hepatology
. 2016 Aug; 64:370-80Slide2
OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
8 weeks
N = 155
12 weeks
N = 155Median
age, years
56
56
Female
34%
37%
Race : white / black
77% / 20%
81% / 15%
Body mass index
26.9
28.0
Genotype
1a Q80K+
1a Q80K-
1b32%43%25%30%45%25%IL28B non-CC genotype74%72%HCV RNA log10 IU/ml, median6.856.83Prior treatment with IFN-based regimen, N (%)RelapseNon-responseIFN-intolerantOther52 (34%)1310111840 (26%)814216Discontinued treatment, N2 (1 lost to follow-up, 1 non-compliance)
Baseline characteristics and patient disposition
OPTIMIST-1
Kwo
P.
Hepatology
. 2016 Aug; 64:370-80Slide3
SVR
12
(HCV RNA < 25 IU/ml), % (95% CI), intent-to-treat *Not superior to historical control
** Superior to historical control
8 weeks
12 weeks
25
50
100
75
83*
(76.3-88.9)
97**
(93.7-99.9)%
8597
Overall
Naïve
Genotype 1a
Q80K+
Experienced
7795739684979297Genotype 1aQ80K-Genotype 1bN15515510311552404946677039390OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosisOPTIMIST-1Kwo P. Hepatology. 2016 Aug; 64:370-80Slide4
SVR
12
(HCV RNA < 25 IU/ml), %, intent-to-treat OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
No impact of race, ethnicity, BMI on SVROPTIMIST-1
93
100
CC
TT
CT
84
97
64
92
96
77
97
< 4M
≥ 4 M41
43
86
862826485610799IL28B genotypeBaseline HCV RNA (IU/ml)255010075%08 weeks12 weeks96NKwo P. Hepatology. 2016 Aug; 64:370-80Slide5
Relapses, overall and according to sub-groups, N (%)
* 7/12 had genotype 1a and prior null response to PEG-IFN + RBV
Resistance testing (population sequencing) of 28 relapsesResistance emergence to SMV, N = 2 (R155K + D1682 + I170T ; I170T)Resistance to SOF (S282T) in 1/25 relapses in the 8-week arm
8 weeks
N = 15512 weeksN = 155
On-treatment
virologic
failure
0
0
Relapse, N (%)
Naïve patientsExperienced-patients
Genotype 1aGenotype 1b
IL28B CCIL28B CTIL28B TT
27 (17%)
15%
23%21%
8%
7%
16%
36%4 (3%)2%5%3%3%0%2%8%OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosisOPTIMIST-1Kwo P. Hepatology. 2016 Aug; 64:370-80Slide6
OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
SMV + SOF 8 weeks
(N = 155)
SMV + SOF 12 weeks
(N = 155)
Any adverse event
97 (63)
103 (66)
Grade 3 adverse event
3 (2)
3 (2)
Grade 4 adverse event
0
1 (1)
a
Serious adverse event
3 (2)
1 (1)
AE with fatal outcome
0
0AE leading to discontinuation00AE in ≥ 10% in either groupNauseaHeadacheFatigue14 (9)26 (17)23 (15)23 (15)22 (14)19 (12)AEs of interestIncreased bilirubinRash (any type)Pruritus (any type)PhotosensitivityDyspnea1 (1)12 (8)9 (6)5 (3)1 (1)1 (1)10 (6)7 (5)2 (1)3 (2)Adverse events, N (%)OPTIMIST-1Kwo P. Hepatology
. 2016 Aug; 64:370-80Slide7
OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
Laboratory abnormalities, N (%)
SMV + SOF 8 weeks
(N = 155)
SMV + SOF 12 weeks
(N = 155)
Increase in bilirubin
Grade 1/2
Grade 3
Grade 4
21 (14)
00
21 (14)
00
Decrease in hemoglobin
Grade 1/2
Grade 3Grade 4
1 (1)
0
0
000Increase in amylaseGrade 1/2Grade 3Grade 419 (12)2 (1)019 (12)7 (5)0Increase in lipaseGrade 1/2Grade 3Grade 412 (8)2 (1)014 (9)1 (1)0OPTIMIST-1Kwo P. Hepatology. 2016 Aug; 64:370-80Slide8
SummaryIn
HCV genotype 1-infected treatment-naïve and treatment-experienced patients without cirrhosis,
12 weeks of SMV + SOF led to SVR12 rates of 97% overall, and demonstrated superiority over the historical control8 weeks of SMV + SOF led to SVR12 rates of 83% overall, and did not achieve superiority compared with the historical controlIn the 12-week arm, SVR12 ≥ 92%
were observed in all subgroups, including those with baseline characteristics historically associated with a poor response to HCV treatment (non-CC IL28B genotype, high HCV RNA at baseline, genotype 1a [with or without Q80K])In the 8-week arm, high SVR12 rates were observed in
patients with baseline HCV RNA < 4 million IU/ml (96%), genotype 1b (92%) and IL28B CC genotype (93%)Patients in the 8-week arm with baseline HCV RNA < 4 million IU/ml had low relapse rates (4%)Treatment with SMV+SOF for 12 or 8 weeks was safe and well tolerated, with no discontinuations due to adverse eventsPatient-reported symptoms and quality of life significantly improved from baseline to the SVR12 time point in both treatment arms
OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis
OPTIMIST-1
Kwo P. Hepatology 2016, Jan 22 (Epub
ahead of print)