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Roth D. EASL 2015, Abs. LP02
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
N = 111GZR + EBR
Placebo
GZR + EBR (Intensive PK)
N = 113
N = 11
GZR/EBR
W12 W16 W28
Objective– SVR12 (HCV RNA < 15 IU/ml) > 45% in immediate and PK groups :
reference rate, with 2-sided significance level of 0.05
≥ 18 yearsHCV infection,
Genotype 1CKD stage 4/5** ± hemodialysisTreatment naïve or pre-treated
with IFN-based regimenCompensated cirrhosis allowed
No HBV or HIV co-infectionOpen label
Resultsnotavailable
Design Randomisation*1 : 1
Double blind
* Randomisation was stratified on diabetes (yes or no) and hemodialysis status (yes or no)** based on eGFR (MDRD equation) : 15-29 ml/min = CKD 4 ; < 15 ml/min = CKD 5GZR 100 mg qd, EBR 50 mg qd, GZR/EBR 100mg/50 mg fixed dose combination 1 pill qd
C-SURFER
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
GZR + EBR(Immediate + PK groups)
N = 122PlaceboN = 113
Mean age, years 57 55Female 25% 29%White / African-American 50% / 45% 43% / 47%
Genotype, n (%)1a1b1 other
63 (52)58 (48)1 (<1)
59 (52)53 (47)1 (<1)
IL28B CC 26.2% 26.5%HCV RNA > 800,000 IU/ml 54.9% 58.4%
Prior treatment history, n (%)NaïveExperienced
101 (83)21 (17)
88 (78)25 (22)
Cirrhosis, n (%) 7 (6) 7 (6)Diabetes, n (%) 44 (36) 36 (32)Dialysis, n (%) 92 (75) 87 (77)
CKD stage, n (%)Stage 4Stage 5
22 (18)100 (82)
22 (19)91 (81)
C-SURFER
Baseline characteristics
Roth D. EASL 2015, Abs. LP02
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
0
25
50
75
100
99.1(95.3-100)
94.3(88.5-97.7)
116 122
ModifiedFull analysis Set
Full analysis Set
SVR12 (HCV RNA < 15 IU/ml), % (95% CI), mITT
%
Primary analysis
100(94.1-100)
61
98.2(90.3-100)
55
97.6(87.1-99.9)
41
100(95.2-100)
75
1a 1b NoYes
DiabetesGenotype
* Genotype 1b, non cirrhotic, CKD stage 5, NS5A RAV at baseline : L31M, at failure : L31M + Y93H
Modified full analysis set excluded patients who died or discontinued for reasons unrelated to treatment
C-SURFER
Relapse 1* 1
Discontinuation unrelatedto treatment
0 6
Roth D. EASL 2015, Abs. LP02
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease Virologic outcome
– SVR12 (99%) > to historical control (45%), p < 0.001
– SVR rates similar in patients with unfavourable baseline charcateristics (African American, IL28B non-CC, cirrhosis)
Resistance associated variants at baseline– NS3 : 36/112 (32.1%) patients : SVR12 in 36/36
– NS5A : 17/115 (14.8%) of patients : SVR12 in 16/17
C-SURFER Roth D. EASL 2015, Abs. LP02
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
GZR + EBRN = 111
PlaceboN = 113 p
Discontinuation due to an adverse event 0 5 (4.4%) 0.026
Serious adverse event 14,4% 16,8% -Drug-related serious adverse event 0 1 -Death 1 (0.9%) 3 (2.7%) -
Adverse events in ≥ 10% in either group HeadacheNauseaFatigueInsomniaDizzinessDiarrhea
17.1%15.3%9.9%6.3%5.4%5.4%
16.8%15.9%15.0%10.6%15.9%13.3%
-----
0.0110.044
Hemoglobin < 10 g/dl* 28.8% 21.2% -
ALT > 2.5 x baseline 0.8% 6.2% -
ALT > 2.5 x baseline 0 4.6% 0.045
Adverse events and laboratory abnormalities, N (%)
* Erythropoietin use : 23% of GZR + EBR group vs 35% of placebo
C-SURFER Roth D. EASL 2015, Abs. LP02
C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease
Summary
– Once daily GZR + EBR for 12 weeks achieved SVR12 of 99% for treatment of HCV genotype 1 infection among patients with chronic kidney disease stage 4-5
• SVR12 of 100% in naïve patients• SVR12 of 95% in experienced patients
– Efficacy was consistent across different subpopulation• Genotypes 1a and 1b• Diabetes• Hemodialysis
– Failure to achieve SVR12 was rare• One patient with genotype 1b relapsed
– Once daily GZR + EBR for 12 weeks was well-tolerated
C-SURFER Roth D. EASL 2015, Abs. LP02
