Presentation is loading. Please wait.

Presentation is loading. Please wait.

Roth D. Lancet 2015; Oct 6; 386:1537-45 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR.

Published byKerry Carr Modified over 8 years ago

Similar presentations

Presentation on theme: "Roth D. Lancet 2015; Oct 6; 386:1537-45 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR."— Presentation transcript:

1 Roth D. Lancet 2015; Oct 6; 386:1537-45 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR + EBR (Intensive PK) N = 113 N = 11 GZR/EBR W12W16W28  Objective –SVR 12 (HCV RNA 45% in immediate and PK groups : reference rate, with 2-sided significance level of 0.05 ≥ 18 years HCV infection, Genotype 1 CKD stage 4/5** ± hemodialysis Treatment naïve or pre-treated with IFN-based regimen Compensated cirrhosis allowed No HBV or HIV co-infection Open label Results not available  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 5 GZR 100 mg qd, EBR 50 mg qd, GZR/EBR 100mg/50 mg fixed dose combination 1 pill qd C-SURFER

2 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease GZR + EBR (Immediate + PK groups) N = 122 Placebo N = 113 Mean age, years5755 Female25%29% White / African-American50% / 45%43% / 47% Genotype, n (%) 1a 1b 1 other 63 (52) 59 (48) 0 59 (52) 53 (47) 1 (<1) IL28B CC26.2%26.5% HCV RNA > 800,000 IU/ml56.6%58.4% Prior treatment history, n (%) Naïve Experienced 101 (83) 21 (17) 88 (78) 25 (22) Cirrhosis, n (%)7 (6) Diabetes, n (%)44 (36)36 (32) Dialysis, n (%)92 (75)87 (77) CKD stage, n (%) Stage 4 Stage 5 22 (18) 100 (82) 22 (19) 91 (81) C-SURFER Baseline characteristics Roth D. Lancet 2015; Oct 6; 386:1537-45

3 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) 116122 Modified Full analysis Set Full analysis Set SVR 12 (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 1a1bNoYes Diabetes Genotype * 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 Relapse1*1 Discontinuation unrelated to treatment 06 Roth D. Lancet 2015; Oct 6; 386:1537-45

4 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease  Virologic outcome –SVR 12 (99%) > to historical control (45%), p < 0.001 – SVR rates similar in patients with unfavourable baseline characteristics (African American, IL28B non-CC, cirrhosis), and in in all subgroups including haemodialysis and non-haemodialysis  Resistance associated variants at baseline –NS3 : 36/112 (32.1%) patients : SVR 12 in 36/36 –NS5A : 17/115 (14.8%) of patients : SVR 12 in 16/17 C-SURFER Roth D. Lancet 2015; Oct 6; 386:1537-45

5 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease GZR + EBR N = 111 Placebo N = 113 p Discontinuation due to an adverse event05 (4.4%)0.026 Serious adverse event14,4%16,8%- Drug-related serious adverse event01- Death1 (0.9%)3 (2.7%)- Adverse events in ≥ 10% in either group Headache Nausea Fatigue Insomnia Dizziness Diarrhea 17.1% 15.3% 9.9% 6.3% 5.4% 16.8% 15.9% 15.0% 10.6% 15.9% 13.3% - 0.011 0.044 Hemoglobin < 10 g/dl*28.8%21.2%- ALT > 2.5 x baseline0.8%6.2%- ALT > 2.5 x baseline04.6%0.045 Total bilirubin > 2.5 -5 x baseline0.9%2.7%- Adverse events and laboratory abnormalities, N (%) * Erythropoietin use : 23% of GZR + EBR group vs 35% of placebo C-SURFER Roth D. Lancet 2015; Oct 6; 386:1537-45

6 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease C-SURFER GZR + EBR N = 111 Placebo N = 113 Initiation of maintenance dialysis, n/N2/250/26 Increase in CKD stage, not on dialysis, n/N4/252/26 Worsening of proteinuria, n48 Mean change from baseline in eGR (mL/min/1.73m 2 ) in patients not on dialysis -At W12 -At follow-up W4 - 0.32 ± 4.79 - 0.13 ± 4.79 - 1.08 ± 3.83 - 1.13 ± 4.85 Renal function monitored events Roth D. Lancet 2015; Oct 6; 386:1537-45

7 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease  Summary –Once daily GZR + EBR for 12 weeks achieved SVR 12 of 99% for treatment of HCV genotype 1 infection among patients with chronic kidney disease stage 4-5 SVR 12 of 100% in naïve patients SVR 12 of 95% in experienced patients –Efficacy was consistent across different subpopulation Genotypes 1a and 1b Diabetes Hemodialysis –Failure to achieve SVR 12 was rare One patient with genotype 1b relapsed –Once daily GZR + EBR for 12 weeks was well-tolerated C-SURFER Roth D. Lancet 2015; Oct 6; 386:1537-45

Download ppt "Roth D. Lancet 2015; Oct 6; 386:1537-45 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR."

Similar presentations

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,
Roth D. EASL 2015, Abs. LP02 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR + EBR (Intensive.

Roth D. EASL 2015, Abs. LP02 C-SURFER Study: grazoprevir + elbasvir in genotype 1 with chronic kidney disease N = 111 GZR + EBR Placebo GZR + EBR (Intensive.
OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind 18-70 years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to pre-treatment with.

OBV/PTV/r + DSV + RBV Placebo Randomisation** 3 : 1 Double blind years Chronic HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Failure to pre-treatment with.
No HBV or HIV co-infection

No HBV or HIV co-infection
C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection GZR/EBR 100/50 mg qd N = 218  Design W12 W24 C-EDGE co-infection Rockstroh JK. Lancet.

C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection GZR/EBR 100/50 mg qd N = 218  Design W12 W24 C-EDGE co-infection Rockstroh JK. Lancet.
SMV 150 + SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.

SMV SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.
SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : 1 18-70 years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥ 10.000.

SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥
UNITY-1 DCV/ASV/BCB No randomisation Open-label UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis  Design W12 ≥ 18 years.

UNITY-1 DCV/ASV/BCB No randomisation Open-label UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis  Design W12 ≥ 18 years.
Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64:948-56 COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN.

Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN.
SIRIUS Placebo LDV/SOF + placebo Randomisation* 1 : 1 Double-blind SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior.

SIRIUS Placebo LDV/SOF + placebo Randomisation* 1 : 1 Double-blind SIRIUS Study: LDV/SOF ± RBV for genotype 1 and cirrhosis with non response to prior.
ION-4  Design LDV/SOF Open-label ION-4 Study: LDV/SOF in HIV co-infection W12 ≥ 18 years Chronic HCV infection Genotype 1 or 4 HCV RNA ≥ 10,000 IU/ml.

ION-4  Design LDV/SOF Open-label ION-4 Study: LDV/SOF in HIV co-infection W12 ≥ 18 years Chronic HCV infection Genotype 1 or 4 HCV RNA ≥ 10,000 IU/ml.
ARV-trial.com C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis Randomisation 1 : 1 Open-label Design W4 W6 W8.

ARV-trial.com C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis Randomisation 1 : 1 Open-label Design W4 W6 W8.
ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.

ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.
OBV/PTV/r Placebo Randomisation** 2 : 1 18-75 years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.

OBV/PTV/r Placebo Randomisation** 2 : years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.
TURQUOISE-I OBV/PTV/r + DSV + RBV Randomisation* 1 : 1 Open-label 18-70 years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN +

TURQUOISE-I OBV/PTV/r + DSV + RBV Randomisation* 1 : 1 Open-label years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN +
ALLY-3  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI DCV 60 mg qd + SOF 400 mg qd Not randomised Open-label ALLY-3 Study: DCV + SOF for.

ALLY-3  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI DCV 60 mg qd + SOF 400 mg qd Not randomised Open-label ALLY-3 Study: DCV + SOF for.
> 18 years Chronic HCV infection Genotype 1 Failure (relapse) to 4, 6 or 8 weeks of GZR/EBR + SOF in C-SWIFT Part A Compensated cirrhosis assessed by liver.

> 18 years Chronic HCV infection Genotype 1 Failure (relapse) to 4, 6 or 8 weeks of GZR/EBR + SOF in C-SWIFT Part A Compensated cirrhosis assessed by liver.
SOF/VEL 400/100 mg qd N = 500 N = 100 W12 Placebo > 18 years Chronic HCV infection Genotype 1, 2, 4, 5 or 6 Naïve or pre-treatment with IFN-based regimen.

SOF/VEL 400/100 mg qd N = 500 N = 100 W12 Placebo > 18 years Chronic HCV infection Genotype 1, 2, 4, 5 or 6 Naïve or pre-treatment with IFN-based regimen.
Forns X. J Hepatology 2015; 63: 564-72 C-SALVAGE Study: grazoprevir + elbasvir + RBV in genotype 1 with failure to PI-based regimen –NS3 and NS5A RAVs.

Forns X. J Hepatology 2015; 63: C-SALVAGE Study: grazoprevir + elbasvir + RBV in genotype 1 with failure to PI-based regimen –NS3 and NS5A RAVs.
SOF/VEL 400/100 mg qd N = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

SOF/VEL 400/100 mg qd N = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

Similar presentations

Ads by Google