Transcript this slide kit - HCV

ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
 Design
Randomisation
1:1
Double-blind
≥ 18 years, HCV genotype 1
Treatment-naïve or treatment-experienced
with IFN or PEG-IFN + RBV or SOF + RBV
± PEG-IFN (exclusion of DAA other than SOF)
HCV RNA > 1 000 IU/mL
No cirrhosis **
No HBV co-infection
HIV co-infection allowed if ARV-naive (HIV
RNA < 1000 c/ml and CD4 ≥ 500/mm3) or on
stable ART with HIV RNA below detection
and CD4 ≥ 200/mm3 (ARV allowed : TDF, 3TC,
FTC, ABC, ZDV, RAL, DTG, RPV)
N = 351
W8
GLE/PIB
GLE/PIB
N = 352
W12
SVR12
SVR12
* Fibroscan® < 12.5 kPa or FibroTest® ≤ 0.48 + APRI < 1
‒ GLE/PIB: 100/40 mg 3 tablets QD
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
 Objectives (SVR12)
– Non-inferiority of the 12-week regimen, by ITT-PS (exclusion of HIV and
prior SOF), with lower margin of the 2-sided CI > 91% (historical rate)
– Non-inferiority of the 12-week regimen, by ITT-PS-PP (ITT-PS +
exclusion of premature discontinuation or virologic failure prior to W8
and missing data in the SVR12 window), with lower margin of the 95%
CI for the difference = 5%
– Non-inferiority of the 8-week regimen, by ITT-PS, with a lower margin
of the 95% CI for the difference = 5%
– Secondary endpoints
– Efficacy in HIV-co-infection and in patients with prior SOF
treatment, by ITT
– Virologic failure and relapse
– Resistance analysis (15% detection threshold)
– Safety
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
Baseline characteristics
GLE/PIB 8W
N = 351
GLE/PIB 12W
N = 352
Median age, years
53
52
Female, %
52
50
Race : White , %
82
86
Median BMI, kg/m2
25
25
Genotype 1a, %
43
42
6.11
6.14
85 / 6 / 9
85 / 7 / 8
IL28B CC, %
29
24
Treatment-experienced, %
IFN-based
SOF-based
38
99
0.8
38
99
1
HIV co-infection, %
CD4/mm3, median
4
644
5
801
6
10
Median HCV RNA, log10 IU/mL
Fibrosis stage (%) : F0-F1 / F2 / F3
PPI use, %
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
Primary Endpoints (SVR12)
12 Weeks GLE/PIB
%
100
99,7
100
8 Weeks GLE/PIB
99,1 *
100
91%
(historical rate)
80
60
- 0,6%
40
20
0
332
331
ITT-PS ITT-PS-PP
335
332
ITT-PS ITT-PS-PP
ITT-PS: ITT population, excluding HIV co-infected and SOF-experienced patients
ITT-PS-PP: ITT-PS population excluding patients with premature discontinuation or
virologic failure prior to W8, and missing data in the SVR12 window
* 1 patient with genotype 1a in the 8W treatment arm experienced on-treatment virologic failure at D29
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
Secondary efficacy endpoints (SVR12): ITT population
8 Weeks
%
100
12 Weeks
99 * 99,7 **
99
99,7
351
336
334
100
100
100
100
1
2
80
60
40
20
0
352
Overall
Mono-infected
15
18
HIV co-infected
SOF-experienced
ITT population: all patients receiving study drug ; none excluded
* 1 patient experienced on-treatment virologic failure, 1 patient discontinued on D2 due to
non-compliance, 1 patient missing SVR12 data
** 1 patient missing SVR12 data
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
Adverse events and laboratory abnormalities, N (%)
GLE/PIB 8W
N = 351
GLE/PIB 12W
N = 352
216 (62%)
234 (66%)
5 (1%)
4 (1%)
Adverse event leading to discontinuation
0
1 (0.3) **
Adverse events in > 10% of patients, %
Headache
Fatigue
19
9
18
12
Laboratory abnormalities
AST grade ≥ 3 (5 x ULN)
AST grade 4
ALT grade ≥ 3 (5 x ULN)
ALT grade 4
Total bilirubin grade 3 (3-10 x ULN)
0
0
0
0
2 (0.6%)
1 (0.3%)
0
0
0
1 (0.3%)
Any adverse event
Serious adverse event *
* On treatment: pneumonia aspiration, atrial fibrillation, angina unstable, radius fracture, transient ischemic
attack, irritable bowel syndrome. Post-treatment: bronchitis, uterine myoma, suicide attempt.
** dandruff, anxiety and amnesia, all deemed not related to therapy.
1 death occurred during post-treatment period due to an unknown cause considered unrelated to study drug
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253
ENDURANCE-1 Study: glecaprevir/pibrentasvir
in genotype 1 without cirrhosis
 Summary
– 99-100% of genotype 1-infected patients without cirrhosis achieved
SVR12 with 8 or 12 weeks of glecaprevir/pibrentasvir (GLE/PIB)
• 8-week treatment was non-inferior to 12-week treatment
(all 3 primary endpoints were met)
• SVR12 rates were high regardless of
–
–
–
–
–
HIV-1 co-infection (limitation: 5% of the study population)
prior treatment experience
baseline HCV RNA
presence of baseline polymorphisms
or other factors
– GLE/PIB was well tolerated
• Only 1 patient (0.1%) discontinued study drugs for adverse event
• No significant laboratory abnormalities
ENDURANCE-1
Zeuzem S. AASLD 2016, Abs. 253