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Design Randomisation 1 : 1 Double-blind W8 W12

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Presentation on theme: "Design Randomisation 1 : 1 Double-blind W8 W12"— Presentation transcript:

1 ENDURANCE-1 Study: glecaprevir/pibrentasvir in genotype 1 without cirrhosis
Design Randomisation 1 : 1 Double-blind W8 W12 ≥ 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 > 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 GLE/PIB SVR12 GLE/PIB SVR12 N = 352 * Fibroscan® < 12.5 kPa or FibroTest® ≤ APRI < 1 GLE/PIB: 100/40 mg 3 tablets QD ENDURANCE-1 Zeuzem S. AASLD 2016, Abs. 253 1

2 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 2

3 Baseline characteristics
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, % 50 Race : White , % 82 86 Median BMI, kg/m2 25 Genotype 1a, % 43 42 Median HCV RNA, log10 IU/mL 6.11 6.14 Fibrosis stage (%) : F0-F1 / F2 / F3 85 / 6 / 9 85 / 7 / 8 IL28B CC, % 29 24 Treatment-experienced, % IFN-based SOF-based 38 99 0.8 1 HIV co-infection, % CD4/mm3, median 4 644 5 801 PPI use, % 6 10 ENDURANCE-1 Zeuzem S. AASLD 2016, Abs. 253 3

4 Primary Endpoints (SVR12)
ENDURANCE-1 Study: glecaprevir/pibrentasvir in genotype 1 without cirrhosis Primary Endpoints (SVR12) 12 Weeks GLE/PIB 8 Weeks GLE/PIB % 100 100 99,7 99,1 * 100 91% (historical rate) 80 60 - 0,6% 40 20 332 331 335 332 ITT-PS ITT-PS-PP 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

5 Secondary efficacy endpoints (SVR12): ITT population
ENDURANCE-1 Study: glecaprevir/pibrentasvir in genotype 1 without cirrhosis Secondary efficacy endpoints (SVR12): ITT population 8 Weeks 12 Weeks 99,7 ** 100 80 60 40 20 99 * 99,7 99 351 336 15 1 352 334 18 2 Overall Mono-infected 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

6 Adverse events and laboratory abnormalities, N (%)
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 Any adverse event 216 (62%) 234 (66%) Serious adverse event * 5 (1%) 4 (1%) Adverse event leading to discontinuation 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) 2 (0.6%) 1 (0.3%) * 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 6

7 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 7

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